L1 - Protein structure & folding Flashcards by Phoebe Snow

Different ways of illustrating protein structure?

Wire frame

Van der Waals surface

Protein backbone

Ribbon/cartoon

Molecular surface

How well did you know this?

Not at all

Perfectly

Wire frame illustration

Shows every bond with a colour at each end that denotes the element

How well did you know this?

Not at all

Perfectly

Van der Waals surface illustration

Atom radii & shows exposure of carbon on the outside

How well did you know this?

Not at all

Perfectly

Protein backbone illustration

Backbone trace

Shows some kind of symmetry about the central region where the active site is

How well did you know this?

Not at all

Perfectly

Ribbon/cartoon illustration

Represents the secondary structure

Red corkscrews – alpha helices

Yellow arrows – point from N terminus to C terminus – show the direction the polypeptide is going

Central domain is made of beta strands forming a barrel

How well did you know this?

Not at all

Perfectly

Molecular surface illustration

Different to the Van der Waals surface as its much smoother & much more representative of the active surface

Can see where the polarity is

How well did you know this?

Not at all

Perfectly

How can we determine protein structure?

X-ray crystallography

Nuclear magnetic resonance (NMR) spectroscopy

How well did you know this?

Not at all

Perfectly

X-ray crystallography

Diffraction patterns obtained from protein crystals are used to reconstruct the coordinates of atoms in the structure

How well did you know this?

Not at all

Perfectly

Nuclear magnetic resonance (NMR) spectroscopy

Magnetic interactions between atomic nuclei spreading through covalent bonds & space can be measured & used to determine connections & distances between protein atoms in the structure while in solution

How well did you know this?

Not at all

Perfectly

How can we know that proteins are dynamic?

Considered to resonate around a normal mode

Often a breathing structure by thermal interactions - Brownian motion hitting the proteins

How well did you know this?

Not at all

Perfectly

What are the non-polar amino acids?

Glycine 
Alanine 
Valine 
Cysteine 
Proline 
Leucine 
Isoleucine 
Methionine 
Tryptophan 
Phenylalanine

How well did you know this?

Not at all

Perfectly

What are the polar amino acids?

Serine 
Threonine 
Tyrosine 
Asparagine 
Glutamine

How well did you know this?

Not at all

Perfectly

What are the positively charged amino acids?

Lysine
Arginine
Histidine

How well did you know this?

Not at all

Perfectly

What are the negatively charged amino acids?

Aspartic acid

Glutamic acid

How well did you know this?

Not at all

Perfectly

What are the layers of protein structure?

Primary - amino acid sequence

Secondary - alpha-helices & beta-strands (turns, loops)

Tertiary - assembly of secondary structural elements

Quaternary - interactions between monomers

How well did you know this?

Not at all

Perfectly

Is the peptide bond planar?

Yes

All atoms are in 1 plane

Is the polypeptide backbone flexible?

Can rotate around the alpha carbon

A protein structure has rigid links and isn’t like a piece of string

Links are joined together at the alpha carbons

Can rotate either side of the alpha carbon link

What are torsion angles on bonds?

Formed by three consecutive bonds in a molecule and defined by the angle created between the two outer bonds

How are torsion angles involved in rotation?

The ability to rotate can be defined – idea of torsion angles on bonds

Have 2: one that looks towards the C terminus (psi angle) and one that looks towards the N terminus (phi angle)

What is a psi angle?

Torsion angle

Look from the alpha-carbon towards carbon

What is a phi angle?

Torsion angle

Look from the nitrogen towards the alpha-carbon

Are the majority of peptide bonds in trans or cis configuration?

Trans

Why are the majority of peptide bonds trans?

Amide proton and the carbon oxygen are pointing in different directions

There is more space like this – they are trying to fight for the same space

Means they face opposite each other – this is defined by the omega angle

What is the omega angle?

The torsion angle measured over the peptide bond, the chemical bond that connects two amino acids

What are the 3 types of torsion angles?

Phi Psi Omega

What degrees can an omega angle be?

can be 0 or 180 (+/- 10) In trans its 180 degrees In rare cases omega = 10 degrees for a cis peptide bond which usually involves proline

How likely are you to get a cis conformation over a trans?

The cis conformation is present in about 1 in 1000 peptide bonds (Trans/Cis = 1000)

Why is the configuration of proline more likely to be cis than other residues?

1 difference is in proline that doesn’t have the amide proton – amide proton is part of the side chain – changes the conformation of the peptide bond Proline is trans 4 times more than cis (Trans/Cis = 4) – is a lot higher for other residues

What is a Ramachandran diagram?

Is a way to visualise energetically allowed regions for backbone torsion angles psi against phi of amino acid residues in protein structure Based upon the steric constraints to psi & phi so the side chain atoms do not overlap in space with other side chain or main chain atoms

Principles of Ramachandran diagrams?

In allowed regions there are no atomic clashes If we take the psi & phi angles you can define the structure of proteins If you analyse the proteins, out of all the angles, you end up with only a very few possible Because of problems with clashing, the proteins can only fold to about 10% of the possible conformations

What does the Ramachandran diagram show us about the freedom of polypeptide chains?

The freedom for polypeptide chain is much less than at first apparent The chain obeys simple rules when folding

Why is the Ramachandran diagram for glycine different?

Has more rotational freedom Big different is glycine that only has a H atom as its side chain – can explore a lot more of the plot Glycine rich regions in proteins are very flexible & have lots of conformations – not accessible to other amino acids

What are side chains chi torsions angles?

The side chain atoms of amino acids are named in the Greek alphabet according to this scheme Potentially around each bond there is a torsion angle Side chains can bring it lots of other complexity The side chain torsion angles are named chi1, chi2, chi3...

What are rotamers?

Rotamers are conformational isomers that differ by rotation about a single σ bond Have certain places that are more common – some angles don’t occur Low energy states are favorable

What do conformational isomers tell us about protein structure?

Have preferred conformations – again proteins are less complex than thought to be

H bonding patterns in the secondary structure?

The peptide group has dual H-bond capacity H-bonds are weak, non-covalent interactions They are directional & specific Each peptide bond can form a H-bond in both directions A network of interactions can hold the polypeptide in a strong & specific framework • Alpha-helices • Beta-sheets Secondary structures form motifs & domains