Lecture 3: Sept 12, 2017

September 12, 2017 10:05 AM

Homework: Lecture Topics:

For Reithmeier's Entire Section: Primary Protein Structure
Ch 1.1-1.4 (Q 9) Secondary Protein Structure
Ch 2 (Q 1(abc), 2(abc), 3, 4, 19b) Tertiary Protein Structure
Ch 4 (Q 6, 7, 17, 20) Quaternary Protein Structure
Ch 5.1-5.8 (Q 2-11)
Ch 6 (Q 3, 4, 7-12, 15)

Pre-Lecture Notes:
Lecture 3/12 - Intro to Proteins and Protein Structure
Dr. Reithmeier lecture 3/12

Lecture Notes: Levels of Protein Structure

The Four Levels of Protein Structure

Primary (1): linear AA sequence

Secondary (2): periodic, repetitive units (alpha-helix, beta-sheet, reverse turn)
Tertiary (3): folding of secondary segments into defined protein structure
Quaternary (4): assembly of protein sub-units

Primary Protein Structures

Example: Insulin
This is an example of two linear structures bound together by disulfide bonds
Alpha chain and beta chain
Amino acids are typically read from the N-terminus (NH end) to the C-terminus (COOH end)

Secondary Protein Structures

Secondary Structure: Alpha-Helix

Here, the NH group of residue i donates H bond back to C=O group of reside i-4
H-bonds that form here are always in competition with water
Water is a byproduct of this reaction
Water can break the bonds very well
Need to pack side chains and minimize the steric clashes --> this config does it
This is a right-handed helix --> most common in nature
This is a hydrophobic structure and is an enthalpy reaction

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 This is a hydrophobic structure and is an enthalpy reaction
Example shown below

Top-View
Green dots are the side chains --> outside is where it's located
Diameter without the side chains is 5 angstroms
It's quite filled inside with a space-filling model
Properties are dictate by the side chains of the chain

Features
Intramolecular H bonds stabilize structure
Always competition with water
Dimensions:
3.6 residues per 360-degree turn
100-degree rotation between adjacent residues (important)
This is very far apart to accommodate the steric forces
1.5 angstrom rise per residue
10 residues together will form a 15-angstrom chain
5 angstrom diameter of the backbone
Right-handed, H bonds face interior with side chains on the periphery of structure
Interact with the surrounding environment, such as lipid bilayers

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Properties
Dependent on the side chains - examples below
Blue is polar, orange is non-polar
Amphipathic: most common alpha-helix
Has two faces: one hydrophobic face and one hydrophilic face
Hydrophilic will interact with water, but hydrophobic folds onto itself

Helix-Helix Interactions
Most of these helices interact with each other
Typically anti-parallel, but possible to have parallel
Angle between helices is usually 50-degress
Small residues are seen at the interface (closest points between them) are usually Gly and Ala
Because they are small and allow packing
Distance between helices depends on AA found in interface region

Beta-Pleated Sheet
Important feature of protein secondary structure
Formed from two or more extended beta-strands of AA, bonded to each other through alternating
intermolecular backbone H-bonds
These sheets are unfolded
Can be anti-parallel and are sheets that stack on top of each other, can be parallel
The H-bonds connect the NH groups with the C=O groups, just like alpha-helices
Can bring distant strands of protein into proximity
Anti-parallel example shown below
There could be a loop that connects both sheets
Note how the side chains alternate: one on bottom, one on top
Alternate up and down to reduce steric forces

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Sugar-Binding Protein
Flat arrows usually shows the beta sheets
Yellow and blue produce the H-bonds
Sugar-binding site is on the inside --> beta sheet is slightly open to allow the sugar in

Summary
Alpha-helix is 1.5 A translation per residue
Beta-sheet is 3.0 A translation per residue
H-bonds are key for both

Beta-Turns
Designates the 4-resiude segment through which the protein chain turns 180 degrees
Can connect helices also
Sometimes called "reverse turns"
Links 2 beta-strands, two helices, strand to helix
The turn is exposed on the outside of the globular protein
Has to go out and come back into the protein, naturally
You get a beta-helix when you have many turns together
You can't have big AA at these positions bc they're restricted
Residues found: frequently Gly, Asn, Pro (usually position 2), Ser
Pro puts a kink in the chain to allow it to turn
Asn and Ser: more polar residues
Asn --> sugars are attached to this typically, if it's a turn, it can bind easily
Ser --> Small AA with a modifiable OH - polar etc

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Beta turns and loops connect helices and strands

Most proteins are both alpha and beta
The lines between the coloured areas are beta turns
Connections can be just 4AA or be much longer and more complex

Tertiary Protein Structure

Defines the final folded structure of the protein

Reps assembly of alpha-helices, beta sheets, beta turns, or disordered regions
Disulfide bonds link diff parts of protein together --> another marker of tertiary

Disulfide Bond
If oxidized, it can be formed in the lumen of the ER
ER is oxidative while cytosol is reductive

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Structure
Segments without periodicity are desc by disordered --> structure defined by sequence
Proteins are dynamic (enzymes) and exist in diff conformational states
It is not one final structure: can be oxygenated or deoxygenated for example (like
hemoglobin)

Quaternary Protein Structure

Hemoglobin is an example of this with the assembly of two or more subunits

Subunits interact through same forces as within indiv subunits
Subunits can be identical or can be all different

Structure
Hemoglobin is a tetramer

Yeast: Ribosome
This has 64 different proteins
These different subunits come together to make a ribosome found in a yeast
Most proteins work as large complexes

Hemoglobin: Tetramer

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Hemoglobin: Tetramer
Hemoglobin is dynamic with conform changes bw oxygenated ( R ) and deoxygenated ( T ) state
Not a static structure --> very important to its function
The oxygen binds to the heme portion of it
If proteins did not change structure, it would likely have no function

Summary

Key role of peptide binds in primary structure

Key role played by hydrogen bonds in secondary structure
Key role played by van der Waals packing and hydrophobic effects in tertiary and quaternary
structure

End of Lecture.

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