Chem 1307 Ch 19.3 Proteins - Secondary Structure

Summary

This script delves into the secondary structures of proteins, focusing on the alpha helix and beta pleated sheets, which are stabilized by hydrogen bonds. It explains how these structures are crucial for protein function, with the alpha helix being more polar and the beta sheet accommodating hydrophobic amino acids. The script also introduces the triple helix found in structural proteins like collagen. It connects the misfolding of beta-amyloid proteins from alpha helices to beta pleated sheets in Alzheimer's disease, illustrating the critical role of protein structure in health and disease.

Takeaways

• 🧬 The secondary structure of proteins refers to the local folding patterns that occur due to hydrogen bonds between amino acids within the same or different peptide chains.
• 🌀 Two common types of secondary structures are the alpha helix and beta pleated sheets, which are crucial for the protein's function and stability.
• 🌈 The alpha helix is characterized by hydrogen bonds between the carbonyl oxygen and the amide hydrogen of the amino acids in the next turn of the helix, forming a spiral staircase shape.
• 📜 Beta pleated sheets form when hydrogen bonds occur between carbonyl oxygen atoms and amide hydrogen atoms of different amino acids, creating a sheet-like structure.
• 🌿 Hydrophobic amino acids are more common in beta pleated sheets, while hydrophilic or polar amino acids are more exposed in alpha helices due to their structural differences.
• 📊 Ribbon diagrams are used to represent the secondary structures of proteins, simplifying the visualization by showing the overall shape rather than individual atoms.
• 🔗 Hydrogen bonds are the primary force maintaining the secondary structures of proteins, such as in alpha helices and beta pleated sheets.
• 🌟 Collagen, a structural protein, contains a triple helix, where three polypeptide chains are intertwined and stabilized by hydrogen bonds, providing strength to tissues like skin, tendons, and cartilage.
• 🧠 Protein misfolding and aggregation, such as the conversion of beta amyloid proteins from alpha helices to beta pleated sheets in Alzheimer's disease, can lead to the formation of insoluble plaques and neuronal dysfunction.
• 💡 The diagnosis of Alzheimer's disease is typically confirmed post-mortem by examining brain slices for atrophy and the presence of neurofibrillary tangles affecting nerve cell transmission.
• 🛑 Neurons do not regenerate quickly, and the death of nerve cells due to protein aggregation and plaque formation in Alzheimer's leads to memory loss and loss of motor function.

Q & A

What is the secondary structure of a protein?

The secondary structure of a protein refers to the local folding patterns of the peptide chain, which are stabilized by hydrogen bonds between the backbone atoms. It includes common structures such as the alpha helix and beta pleated sheets.

What are the two most common types of secondary structures in proteins?

The two most common types of secondary structures in proteins are the alpha helix and beta pleated sheets.

How are alpha helices formed in proteins?

Alpha helices are formed by hydrogen bonds between the oxygen of the carbonyl groups and the hydrogen of the NH groups of the amide bonds in the next turn of the helix, which gives the peptide chain a helical shape.

What interactions are responsible for the formation of beta pleated sheets in proteins?

Beta pleated sheets are formed by hydrogen bonds between the carbonyl oxygen atoms and the hydrogen atoms in the amide group, which bend the polypeptide chain into a sheet-like structure.

What is the difference between alpha helices and beta pleated sheets in terms of amino acid exposure?

Alpha helices tend to have more polar or hydrophilic amino acids exposed due to their tight interaction, while beta pleated sheets may have more hydrophobic amino acids tucked away from the aqueous environment.

What is a triple helix and where is it commonly found?

A triple helix is a secondary structure found in structural proteins like collagen, where three polypeptide chains are woven together with hydrogen bonds holding the chains together, providing additional strength.

How does the representation of proteins change when using a ribbon diagram?

In a ribbon diagram, the protein is represented with a general structure rather than individual atoms, showing the secondary structures like alpha helices and beta pleated sheets as ribbons, which simplifies the visualization of large proteins.

What is the significance of the N-terminus and C-terminus in the context of protein structure?

The N-terminus and C-terminus are the beginning and end of a protein chain, respectively. They can be identified in protein diagrams to understand the directionality of the amino acid chain and are important for the overall three-dimensional structure.

How can changes in protein secondary structure lead to disease?

Changes in protein secondary structure, such as the conversion of alpha helices into beta pleated sheets in Alzheimer's disease, can cause proteins to misfold and aggregate, leading to the formation of insoluble plaques that disrupt normal cellular functions and contribute to disease pathology.

What is the role of beta amyloid proteins in Alzheimer's disease?

In Alzheimer's disease, beta amyloid proteins change from their normal alpha helical shape to beta pleated sheets, forming insoluble aggregates that accumulate as plaques, which are implicated in the disruption of neuronal signaling and contribute to the disease's progression.

How can the diagnosis of Alzheimer's disease be confirmed?

The official diagnosis of Alzheimer's disease can only be done post-mortem by examining brain slices for atrophy and the presence of neurofibrillary tangles. However, symptoms like memory loss and loss of motor function can be used for an unofficial diagnosis.

Outlines

00:00

🌀 Secondary Structure of Proteins

This paragraph introduces the concept of protein secondary structure, which is the pattern that arises from hydrogen bonds between atoms in the amino acid backbone. It explains that these interactions are localized and not covalent bonds. The two most common types of secondary structures are the alpha helix and beta pleated sheets, with a brief mention of the triple helix found in structural proteins like collagen. The alpha helix is characterized by hydrogen bonds between the carbonyl oxygen and the hydrogen of the amide bond, forming a spiral staircase shape. The paragraph also discusses the representation of these structures using ribbon diagrams and the significance of hydrogen bonds in forming the alpha helix.

05:00

📜 Beta Pleated Sheets and Hydrophobic Interactions

This paragraph delves into the secondary structure of beta pleated sheets, highlighting the formation of hydrogen bonds between carbonyl oxygen atoms and hydrogen atoms in the amide group of different amino acids, resulting in a sheet-like structure. It contrasts the beta pleated sheets with alpha helices, noting the presence of hydrophobic amino acids in the former and hydrophilic or polar amino acids in the latter. The paragraph also describes the use of ribbon diagrams to represent the secondary structures in proteins, with arrows indicating the direction of the amino acid chain from the N-terminus to the C-terminus.

10:03

🔍 Triple Helix and Protein Misfolding in Disease

This paragraph discusses the triple helix, another type of secondary structure found in structural proteins such as collagen. It explains that the triple helix is formed by three polypeptide chains held together by hydrogen bonds, providing strength to connective tissues. The paragraph then connects protein structure to disease, using Alzheimer's disease as an example. It describes how beta-amyloid proteins, normally in an alpha-helical form, can misfold into beta pleated sheets, leading to the formation of insoluble plaques that contribute to neuronal dysfunction and death. The paragraph emphasizes the irreversible nature of neuronal loss and the impact on memory and motor functions.

15:04

🧠 Alzheimer's Disease and Protein Aggregation

The final paragraph focuses on the role of protein misfolding in Alzheimer's disease. It describes the transformation of beta-amyloid proteins from a normal alpha-helical shape to insoluble beta-pleated sheets that aggregate into plaques, both inside and outside neurons. These plaques disrupt neuronal signaling and contribute to cell death and brain atrophy. The paragraph explains that while the official diagnosis of Alzheimer's can only be made post-mortem by examining brain tissue for neurofibrillary tangles, symptoms such as memory loss and motor function decline can be used for an unofficial diagnosis. The summary concludes by reiterating the importance of understanding protein secondary structures in the context of disease.

Keywords

💡Secondary Structure

The secondary structure of a protein refers to the local folding of its peptide chains into specific conformations, primarily stabilized by hydrogen bonds. This concept is central to the video as it sets the foundation for understanding how proteins achieve their functional shapes. Examples from the script include the alpha helix and beta pleated sheets, which are the most common types of secondary structures.

💡Alpha Helix

An alpha helix is a right-handed coiled structure formed by hydrogen bonds between the oxygen of the carbonyl group and the hydrogen of the amide bond in the next turn of the helix. It is a key secondary structure in proteins and is mentioned in the script as a twisted structure that contributes to the protein's overall shape and function.

💡Beta Pleated Sheets

Beta pleated sheets are a type of secondary structure where hydrogen bonds form between the carbonyl oxygen atoms and the hydrogen atoms in the amide group, bending the polypeptide chain into a sheet. The script describes these as a significant component of protein structure, often containing more hydrophobic amino acids compared to alpha helices.

💡Hydrogen Bonds

Hydrogen bonds are a type of intermolecular force that plays a crucial role in stabilizing the secondary structure of proteins. In the script, hydrogen bonds are described as the main interaction between amino acids in both alpha helices and beta pleated sheets, contributing to their respective shapes.

💡Globular Proteins

Globular proteins are compact, roughly spherical proteins that perform specific functions. The script mentions these proteins in the context of having secondary structures like alpha helices and beta pleated sheets, which contribute to their overall three-dimensional shape and function.

💡Tertiary Structure

The tertiary structure of a protein refers to its three-dimensional shape resulting from the folding of its peptide chain, which includes both secondary structures and additional interactions. The script discusses how the combination of alpha helices and beta pleated sheets contributes to the formation of the tertiary structure.

💡Triple Helix

A triple helix is a type of secondary structure found in proteins like collagen, where three polypeptide chains are intertwined and held together by hydrogen bonds. The script mentions the triple helix as a unique structure that provides added strength to structural proteins.

💡Aqueous Environment

An aqueous environment refers to a water-based medium where many biological processes, including protein folding, occur. The script discusses how the presence of water influences the distribution of hydrophobic and hydrophilic amino acids in protein structures like alpha helices and beta pleated sheets.

💡Ribbon Diagram

A ribbon diagram is a simplified representation of protein structure where the peptide backbone is depicted as a ribbon. The script uses this term to describe how proteins are often visualized, focusing on the secondary structures like alpha helices and beta pleated sheets rather than individual atoms.

💡Alzheimer's Disease

Alzheimer's disease is a neurodegenerative disorder characterized by memory loss and cognitive decline. The script discusses how the misfolding of beta amyloid proteins from an alpha helical shape to beta pleated sheets contributes to the formation of insoluble plaques, which are a hallmark of Alzheimer's disease.

💡Neurofibril Tangles

Neurofibril tangles are abnormal structures found in the neurons of individuals with Alzheimer's disease. The script mentions these tangles in the context of post-mortem diagnosis, where they are observed alongside brain atrophy and the presence of beta amyloid plaques.

Highlights

The secondary structure of a protein is defined by the hydrogen bonds between atoms in the amino acid backbones, forming local structures.

Two common types of secondary structures are the alpha helix and beta pleated sheets, with the former being common in globular proteins and the latter in structural proteins.

Collagen, a structural protein, contains a triple helix, which is another type of secondary structure.

The alpha helix is characterized by hydrogen bonds between the carbonyl oxygen and the hydrogen of the amide bond in the next turn of the helix.

Hydrogen bonds in the alpha helix give it a helical, spiral staircase shape.

Ribbon diagrams are used to represent proteins, simplifying the visualization by showing secondary structures without individual atoms.

Beta pleated sheets form when hydrogen bonds occur between carbonyl oxygen atoms and hydrogen atoms in different regions of the polypeptide chain.

Hydrophobic amino acids are more common in beta pleated sheets, while hydrophilic or polar amino acids are more exposed in alpha helices.

The direction of the amino acid chain in beta pleated sheets is indicated by arrows in ribbon diagrams.

The triple helix in structural proteins like collagen is formed by three polypeptide chains held together by hydrogen bonds, providing strength.

Hydrogen bonds are the dominant force in the triple helix, similar to the alpha helix.

Protein malfunction or structural issues can lead to diseases, such as Alzheimer's, where protein secondary structures are affected.

In Alzheimer's disease, beta amyloid proteins change from alpha helices to insoluble beta pleated sheets, forming plaques that disrupt neuronal function.

Neurofibril tangles in neurons, associated with Alzheimer's, affect nerve cell transmission and contribute to the disease's progression.

The diagnosis of Alzheimer's can only be confirmed post-mortem by examining brain slices for atrophy and the presence of neurofibril tangles.

Unofficial diagnosis of Alzheimer's is based on symptoms like memory loss and loss of motor function.

The transition of beta amyloid proteins from alpha helices to beta pleated sheets in Alzheimer's leads to the formation of plaques and neuronal death.

Transcripts

in the next section of this chapter we

will discuss the secondary structure of

proteins the secondary structure of a

protein describes the structure that

forms when amino acids form hydrogen

bonds between the atoms in their

backbone and the atoms on the same or

another peptide chain so basically you

have some interactions between amino

acids now we're not talking about the

covalent linkage between amino acids

we've already established that but we're

looking at now interactions between

different amino acids in different

regions but those regions are pretty

localized two common types include the

alpha helix and the beta pleated sheets

and of course we're looking at the

globular proteins or those proteins that

carry out very particular or specific

functions the structural proteins might

have something called a triple helix and

we'll see that a little bit later so in

this lesson we're going to describe the

two most common types of secondary

structure for a protein the helix and

the beta pleated sheets right and then

we're going to describe the structure of

collagen collagen contains the triple

helix

because it is a structural protein

in the diagram to the right you will see

an example of the alpha helix

the baited pleated sheets and then they

combine to create a functional protein

this is more of a three-dimensional

structure right our tertiary structure

so we're going to discuss these first

two which will interact later right to

create the tertiary structure

let's start by describing the

interactions that occur between the

amino acids when we have an alpha helix

in our protein

in the secondary structure of an alpha

helix hydrogen bonds form between the

oxygen of the carbonyl groups and the

hydrogen of nh groups of the amide bonds

in the next turn of the alpha helix so

the main intermolecular force that is

occurring between localized amino acids

for the alpha helix and this kind of

twisted structure

is the hydrogen bond okay so hydrogen

bonds are the most significant

interaction between amino acids to form

the alpha helix the formation of many

hydrogen bonds along the peptide chain

gives a helical shape of a spiral

staircase okay so this basically this

little twisted

region is going to be our alpha helix

they draw what's called the ribbon

diagram where those amino acids are kind

of just drawn as

you know like solid

ribbons and over here on the side here

you start to see the individual atoms

and the individual amino acids

the reason why we draw ribbon diagrams

is because when proteins are very large

they actually have a ton of atoms so

it's a little bit hard to distinguish

between amino acids anyways but you will

see different uh representations of a

protein so you have your molecules right

and then the ribbon diagram showing your

alpha helix

let's take a quick look at the actual

hydrogen bond so

here it mentions that you have an oxygen

of the carbonyl that is going to

hydrogen bond

with the hydrogen of the next amino

acids um amide bond right so here is our

amide bond which is the carbon of the

carbonyl

from the previous amino acid bonded to

the nitrogen of the ammonium region

right and so this nitrogen from the next

amino acid is going to interact well not

the nitrogen itself but the hydrogen

which is partially positive is going to

interact with the partially negative

oxygen of the carbonyl and of course we

said that the interaction is via

hydrogen bonding

so let's take a look at the beta pleated

sheets in the secondary structure of a

beta pleated sheet hydrogen bonds form

between the carbonyl oxygen atoms and

the hydrogen atoms in the amide group

bending the polypeptide chain into a

sheet

so let's take a look at that interaction

so you have your peptide chain here and

so of course this peptide chain is

starting to fold right and we said that

the fold is happening in localized

regions so this carbonyl oxygen is going

to hydrogen bond to

the hydrogen of the nitrogen

participating in the amide bond of a

different amino acid in a different

region not necessarily

right next to it right like the actual

peptide bond so remember these are only

interactions not covalent linkages

so we have our hydrogen bond there

the difference between the secondary

structure of the beta plated sheets and

those of the alpha helices is the

presence of hydrophobic amino acids if

you have hydrophobic amino acids they

probably want to be tucked away in this

chain here right away from the water so

for beta plated sheets you'll probably

see more hydrophobic amino acids than in

the alpha helices for the alpha helix

you'll see

a tight interaction so more polar right

more hydrogen bonds but also you will

see that there is a lot of amino acids

out here that are going to be exposed

to the water right we're in an aqueous

environment so you'll probably see more

hydrophilic amino acids or more polar

amino acids in the

alpha helices

so as we previously mentioned we can

represent the structure of a protein

using the ribbon model or the ribbon

diagram the most common

features of the ribbon diagram are the

secondary structures including the alpha

helix right you don't see individual

atoms anymore only a general structure

right so it's like if i zoomed out and

kind of looked at the molecule by

zooming out you just kind of see

everything combined together creating

this organization so you'll see the

ribbon model um for the alpha helix

right and then also for the beta pleated

sheets for the beta pleated sheets they

show you arrows to represent the

direction of the amino acid chain so

this is the n-terminus and then we're

going this way to the c terminus

and then some of these will have many

beta plated sheets until you get to the

c terminus right so once you start to

kind of put this together or the protein

itself starts to put itself together

you'll see many beta plated sheets and

alpha helices

so a protein with alpha helices and beta

pleated sheets is found here

you can look for the n terminal usually

they will label it for you

and it will be in one of these

non

helical or

sheeted

regions so they're just kind of

represented by the strand itself and you

will also be able to find the c terminus

the end of the protein they're not

labeled in this particular diagram and

it's really hard to see the c and the n

terminus now if you're looking at the

three-dimensional structure you might be

able to um use a program that shows the

three-dimensional structure that will

allow you to rotate the molecule to find

the beginning and the end of the chain

or also help you to kind of see what's

on the back here well we know it's a

beta pleated sheet but what's the

direction of that strand in the back

right that sheet so you can use some

different programs to help you visualize

in three dimensions and basically kind

of turn the molecule around

another type of secondary structure

includes the triple helix we talked a

little bit about how the triple helix

was present in a lot of structural

proteins so in a triple helix three

polypeptide chains are woven together

hydrogen bonds hold the chains together

giving the polypeptide the added

strength of typical structural proteins

like collagen connective tissue skin

tendons and cartilage

so here you have kind of like the

winding of the three polypeptide chains

right it's starting to wind and then

over here it's really gotten tight

collagen fibers are triple helices of

polypeptide chains held together by

hydrogen bonds so of course just like in

the alpha helix which only involves one

strand the main type of interaction

among amino acids

in different regions right here you have

three different chains interacting

with one another through hydrogen bonds

so the hydrogen bond is the dominant

force here

so let's try this learning check

indicate the type of protein structure

in the primary

sequence the alpha helix the beta plated

sheet and the triple helix

okay so letter a polypeptide chains held

side by side by hydrogen bonds

sequence of amino acids in a polypeptide

chain

corkscrew shape with hydrogen bonds

between amino acids and three peptide

chains woven like a rope okay so let's

match the

type of structure to the description so

polypeptide chains held side by side by

hydrogen bonds so this is going to be

our beta pleated sheets right

side by side to create those um sheets

so here we're going to say this is a

right

and then the sequence of amino acids in

a polypeptide chain this is going to be

the primary sequence

and then the corkscrew shape with

hydrogen bonds between amino acids

that's the alpha helix so this is c and

then of course the three polypeptide

chains woven like a rope is the triple

helix

let's see if we were correct

okay so the polypeptide chains held side

by side by hydrogen bonds

are in fact the beta pleated sheets the

sequence of amino acids in a polypeptide

chain is the primary structure of the

protein a corkscrew shape with hydrogen

bonds between amino acids is the alpha

helix and then the three peptide chains

woven like a rope is the triple helix

in the beginning of our lessons on

proteins we talked a little bit about

how

any time a disease state is occurring we

will look to see if there is a protein

involved a lot of the time you have a

malfunction of a protein or a structural

problem with that protein which causes

it to malfunction

let's take a look at an example of a

protein secondary structure and how this

can lead to disease

alzheimer's disease is a form of

dementia in which a person has

increasing memory loss and inability to

handle daily tasks

so how does this come about how does

this disease arise

in the brain of a normal person small

beta amyloid proteins made up of 42

amino acids exist in the alpha helical

form

in the brain of a person with

alzheimer's disease the beta amyloid

proteins change shape from the normal

alpha helices which are soluble

to the sticky beta pleated sheets which

are insoluble right they form clusters

of insoluble protein fragments called

plaques

so these plaques continue to build until

eventually the neuron can't handle it so

one they can't pass the neuronal signal

and two they eventually die

neuron cells don't replenish themselves

quickly like say skin cells right skin

cells will regenerate quite easily and

quite quickly

however the neurons don't so once those

nerve cells die they don't come back so

a lot of the regions that are affected

by these

by this disease

and the beta amyloid protein problem is

the memory region right the hippocampus

of the brain and other motor regions

right those that are responsible for our

normal functions so somebody that dies

of alzheimer's will actually die because

their motor functions are not working

for example they can no longer breathe

because the nerves aren't firing to send

the signal to tell the body to breathe

or to swallow or to digest and so all of

those body functions are starting to

shut down

unfortunately

the diagnosis of alzheimer's

can only be done post-mortem because

slices of the brain must be taken and

studied and basically we look at the

atrophy or the brain kind of shrinking

or starting to die

and then we look for the presence of

neurofibril tangles

in the neurons that affect the

transmission of the nerve cells so again

the official diagnosis can only be done

postmortem but other

symptoms can be used to unofficially

diagnose someone as having alzheimer's

disease like memory loss

and loss of motor function

so let's take a look at these diagrams

here you have a normal or a healthy

beta amyloid that is found in its alpha

helical form

but with somebody that has alzheimer's

disease or that's in a disease state

these alpha helices are not necessarily

folded correctly and instead they are

converted into the beta pleated sheets

so here's our diseased

state right the alzheimer's

and of course we said that now that

alpha helix has been converted into beta

pleated sheets which create these large

plaques the large plaques will prevent

the nerve impulse from firing from

neuron to neuron right so here you have

your healthy

neuron

if you look closely at the diseased

state here the cell contains not only

the plaques inside the cell right but

you also have a buildup of these beta

amyloid plaques outside the cell so it

affects transmission in two ways so it's

blocking transmission here so receiving

the signal from the previous cell

but also you have way too much stuff in

here and these large tangles that are

found within the cell um are actually

going to prevent the transmission as

well and again eventually these cells

will die because they can't handle all

of those um beta plated sheets right

those plaques that are formed

those cells don't regenerate quite

quickly and so then you start to have

atrophy of the brain

memory loss and of course motor

functions are also lost

in patients with alzheimer's disease

beta amyloid proteins change from a

normal alpha helical shape to beta

pleated sheets that are insoluble

aggregates they form plaques right they

aggregate together they stick to one

another

and of course these plaques remain in

the in the neuron and of course

eventually the neuron will die

so this concludes our lesson on the

secondary structure of a protein in the

next lesson we'll talk about the

tertiary structure