Protein Structure and Folding

What contributes to a protein’s structure

Amino acids’ distinct side chains

How are stable, complex 3D structures formed?

By the folding of linear chains of amino acids

What drives protein folding and interactions with other molecules?

Covalent and non-covalent interactions between amino acid functional groups

What is the primary protein structure?

The linear sequence of amino acids encoded by DNA

What is the secondary protein structure?

Periodic, regular structures

What are the 3 secondary protein structures

• Alpha helix

• Beta strands

• Beta turns

What is the tertiary protein structure?

Folding of secondary structures into a define protein motifs and domains

What is the quaternary protein structure?

Arrangement of multiple subunits of distinct identical or identical polypeptide chains held together covalently or non-covalently

How are amino acids joined?

Enzymatically in a condensation reaction

What is the start of the polypeptide chains

Amino terminal end (N-terminus)

AA #1

What does the backbone of the polypeptide chain consist of?

Peptide bonds

The alpha carbon of each amino acid

What does each amino acid contribute to the structure?

A variable, distinct R side chain that is not part of the backbone

Which amino acid contributes a side chain that is part of the backbone?

Proline

What are peptide bonds?

Polar, uncharged bonds

Characteristics of peptide bonds

• characteristics of double bond

• experience resonance

• no rotation around the bond

• rigid

• flat, planar structure

Characteristics of phi and psi bonds

• rotation allowed around bond

• angles range from -180 to +180 degrees

When are steric clashes minimized?

When the bulky side chains are trans to one another

What is a phi bond?

The bond linking the amide to the alpha carbon

What is a psi bond?

The bond linking carbonyl to the alpha carbon

Which amino acid has the greatest impact on the path of the polypeptide backbone and why?

Proline

• creates ring between side chain and amino

• no rotation around phi bond

What is the alpha helix?

Right-handed helix with the side chains pointing out from the coil

Where do intra-strand hydrogen bonds form in alpha helices?

Between backbone residues down centre of helix

Which groups are involved in hydrogen bonding in alpha helix?

C = O from one to a N-H group 4 residues away (i & i+4)

How many residues are there per 360 degree turn?

3.6 residues

How high is each residue in the alpha helix?

1.5A

Explain hydrogen bonding in beta strands

H-bonds link the backbone carbonyls and amines of nearby/distant beta strands

How is steric hindrance prevented in beta strands?

By R groups alternating

What are the 3 ways a beta strand may run?

• Parallel

• Antiparallel

• Mixed in directionality

What is the role of a beta sheet?

Can bring distant parts of the protein together

What is a beta turn?

A 4 residue segment that allows the polypeptide chain to turn 180 degrees

Where can beta turns be found?

On the surface of globular proteins, connecting secondary structures

Explain hydrogen bonding in beta turns

Form between carbonyl oxygen at position 1 and amine hydrogen at position 4

Which amino acid is common at position 2 in beta turns?

Proline

Which amino acids are frequently seen in beta turns?

• Glycine

• Asparagine (sugars)

• Serine (phosphate group)

What are motifs/domains?

Commonly seen structures

What is the role of non-covalent interactions and cofactors in higher levels of organization?

Bringing distinct regions together

What is the role of disulfide bonds in tertiary and quaternary structures?

Stabilization

How are tertiary structures formed?

When secondary structures come together, joined by flexible linker segments

Where are zinc fingers found?

In DNA-binding proteins

What is the role of zinc fingers?

Contain zinc ions that coordinate distant side chains, stabilizing domains

Proteins with similar structures…

May have similar domains

What does analysis of a protein’s sequences allow researchers to do?

Predict where a functional domain may exist based on the known sequence of other domains

How do different subunits arise in quaternary structures?

• From multiple genes

• Due to post-translational cleavage of precursers

How are larger macromolecular strucutures formed?

Interactions between polypeptide chains