23. Modular Structure of Proteins

Question 1

Describe Amino acids? (6pts)

Answer 1

1. There are 20 amino acids
2. Amino acids fall into categories defined by their properties e.g hydrophobic is non-polar and polar groups are aromatic.
3. Individual amino acid properties provided by the variable side chain determines inter and intra molecular behaviour.
4. The structural behaviour of a polypeptide chain is conferred by the chemical composition of the consistent amino acids. For example carboxyl groups are electrostatic.
5. Structure of a protein is dynamic and driven by the requirement to form a structure with the lowest free energy.
6. Molecular behaviour determines the folding of the polypeptide chain.

Question 2

Describe a motif?

Answer 2

A combination of two or more secondary structures to form a recognisable localised folded arrangement of structures.

Question 3

Describe a domain?

Answer 3

Defined as a more complex structure at the tertiary or quaternary level often involving interaction between distant parts of a protein or motifs.

Question 4

Describe Motifs and domains? (9pts)

Answer 4

1. Motifs and domains are an independent order of structure.
2. These can be identified within the overall tertiary or quaternary structure.
3. They are an independent order of structure different from primary, secondary, tertiary and quaternary.
4. Motifs are organised or combined into larger structural and functional domains.
5. Domains more clearly define a functional unit than a motif but both are evolutionary conserved and are modular in nature.
6. Functional domain is typically larger and can be a continuous segment of a polypeptide chain.
7. A motif is a minimum arrangement of secondary structure combining folds and it is a small structural unit that can be recognised in a variety of proteins.
8. A domain is a more complex structure that has a tertiary or quaternary structure of its own.
9. Larger proteins are composed of several domains. Domains are functional units that are found across different genes and phyla that have evolved over time.

Question 5

Describe a Beta Barrel motif?

Answer 5

Beta strands wrapped around to form a circular tunnel

Question 6

Describe a Beta-alpha-beta motif?

Answer 6

Parallel strands of a beta sheet interlinked with an alpha helix

Question 7

Describe DNA binding motifs?

Answer 7

Helices can be inserted into the major grove of DNA in a sequence specific matter

Question 8

Describe membrane bound receptors?

Answer 8

1. Functional domain
2. Come in several forms but most commonly as bundles e.g bundles of alpha helices.
3. The transmembrane domain arrangement of alpha helices is common and is found in rhopsin and TSHr.

Question 9

Describe domain shuffling?

Answer 9

Domain shuffling in the genome results in modular units of function being conserved but shuffled between genes.

Question 10

Describe Haemoglobin evolution?

Answer 10

Haemoglobin has 4 chains. Each chain of haemoglobin has a tertiary structure very similar to that of the single myoglobin chain, strongly suggesting evolution from a common ancestral 02 binding polypeptide.

Question 11

Describe transcription factors? (4pts)

Answer 11

1. Transcription factors are proteins that bind to DNA and regulate transcription.
2. There are many different transcription factors but each contain a small number of conserved motifs which combine to form domains that interact with the DNA.
3. These motifs are conserved across all phyla.
4. These motifs form DNA binding domains that allow the regulatory function of their respective proteins.

Question 12

Describe Alpha helices? (3pts)

Answer 12

1. An alpha helix can fit within the major grove of DNA- comprising the recognition helix.
2. The amino acid sequence of a DNA binding motif provides specificity.
3. Different DNA binding domains and motifs present the binding helix using different arrangement of the structural motif.

Question 13

Describe the Helix-loop-helix motif? (5pts)

Answer 13

1. Bind DNA only in the dimeric form
2. exist as hetro (different monomers) and homodimers (identical monomers)
3. The central portion is made from overlapping helices that form a structure enabling dimerization.
4. The terminal part of the lower opposing helices contain basic amino acids that interact with the major grove of the DNA.
5. e.g mad, max.

Question 14

Describe the Leucine Zipper motif?

Answer 14

1. The motif is formed from 2 contiguous alpha helices and is a dimeric protein formed from 2 polypeptide chains.
2. The dimers zip together in the top stalk to form a short coiled-coil which is held together by hydrophobic interactions down opposing sides of the helix.
3. The amino acids dominate the lower part of the helix forming a motif and interact with the DNA major grove.
4. Heterodimerisation expands the regulatory potential of Leucine zippers.

Question 15

Describe the helix-turn-helix motif?

Answer 15

1. Consists of 2 short helices orientated at right angles to each other and connected by a “turn”.
2. The motif is found in both prokaryotic and eukaryotic DNA binding proteins e,g CRO repressor and homebox proteins.
3. The CRO protein is a homodimer. CRO recognises palindromic sequences and by binding DNA represses transcription.
4. Only the recognition helix interacts with the nucleotide sequence itself and like other DNA binding motifs it is located within the major grove.

Question 16

Describe the zinc finger motif? (3pts)

Answer 16

1. This motif is an alpha helix and a beta sheet held together by non-covalent interactions with zinc.
2. The alpha helix of each motif interacts with the major grove of DNA and recognises a specific DNA sequence.
3. The proteins that have zinc fingers include many hormone receptors such as vitamin d receptors.