BIOL 1510 Chapter 4

Why are peptide bonds planar?

Because of resonance, which gives them a partial double bond character

Can peptide bonds rotate?

No! Rotation is restricted by partial double bond character

What bonds can rotate in the peptide backbone?

N-C and C-C bonds that are no involved in the peptide bond itself

Is bond rotation easy in peptides?

No, most rotation angles are restricted by steric hinderance

Ramachandran plot

Depicts which rotation angles are allowed and which ones aren’t

• darker color=allowed

• lighter color=disallowed

How are alpha helices formed?

Hydrogen bonds between main chain atoms (O-H)

How many residues are present in each alpha helix?

3.6 residues

Where are the R groups positioned in an alpha helix?

Point outwards

What direction does an alpha helix wind in?

right-handed helix

Dipole moment in alpha helix

Dipole forms from N terminus to C terminus

Beta strand

Formed by hydrogen bonds between main chain O and H atoms

Beta sheet

When beta strands hydrogen bond together

Parallel beta sheets

N terminus lined up with N terminus and vice versa

Antiparallel beta sheet

N terminus lined up with C terminus

Which form of beta sheet (parallel or antiparallel) is stronger and why?

Antiparallel is more stable because the hydrogen bonds between beta strands are head on, leading to stronger interactions

Beta turn

Rounding of a corner that connects two strands of an antiparallel beta sheet

• two types: type I and type II

What amino acids are involved in a beta turn?

glycine or proline

Why is glycine good for beta turns?

small and flexible amino acid

Why is proline good for beta turns?

Bulky but can assume a cis or trans configuration

Position of R groups in a beta sheet

R groups protrude in opposite direction from the zig zag pattern

Fibrous proteins

long stringy proteins that are often important for structure

Fibrous protein structure

Usually made of tight alpha helices

• can have repeat sequences of glycine, proline, hydroxy-proline

Globular protein

Balled up and compact proteins often important for cellular functions

Ways to represent protein structure

ribbon representation, surface model, ball and stick model, space-filling model

Ribbon representation

Mostly secondary structures

Surface model

This thing

Ball and stick model

Can clearly see atoms and functional groups

Space filling model

Similar to surface model

Beta-alpha loop

A loop formed by a repeating pattern of

1. beta strand

2. alpha helix

3. beta strand

Alpha-beta barrel

A type of fold when multiple beta-alpha loops come together

Supersecondary structure

3D structure consistent of multiple secondary structures

Motif

Any simple or complex distinct folding patter

• supersecondary structure

Domain

A distinct structural unit that may have a separate function

Do all proteins have ordered secondary structures?

No!

Intrinsically disordered domains

Parts of a protein that don’t have a set protein structure

What is the purpose of intrinsically disordered domains?

Allows for morphing/conformational change

Proteostasis

homeostasis but for proteins

Chaperone proteins

proteins that create favorable microenvironments that allow naive proteins to fold properly

Chaperonins and heat shock proteins

helper proteins that interject during protein misfolding and help proteins refold into the correct form

Anfinsen’s classical experiment

1. denatured and reduced ribonuclease A—>denaturing and reducing agent added

2. Both agents were slowly removed

3. Ribonuclease A activity was measure and found that it rose over time

Conclusion of Anfinsen classical experiment

Protein refolded itself!

Techniques to determine protein structure

• circular dichroism

• NMR

• X-ray crystallography

• cryo-EM

Circular dichroism

A spectroscopy technique that allows you to determine the fraction alpha helices and beta sheets

NMR spectroscopy

3D NMR used to determine small protein structure by placing it in magnetic field

X-ray crystallography

protein crystals bombarded with x-rays to create a diffraction pattern. Then, the pattern is analyzed to generate a model

cryo-EM

determines structure of large complexes

What secondary structure is an extended conformation of the polypeptide chain?

beta sheets