Protein Structure

Question 1

Name the functions of proteins within a cell and name examples of how

Answer 1

Defence, Signalling, Transport, Catalysis, Movement, Structure and Regulation
Eg: Membrane transports, Receptors, Antibodies

Question 2

What do structural proteins provide?

Answer 2

Mechanical support

Question 3

What do transcription factors do?

Answer 3

Switch genes on/off

Question 4

What do enzymes do?

Answer 4

Accelerate rate of metabolic reactions

Question 5

What do motor proteins do?

Answer 5

Transport cellular cargoes/organelles, generate muscular contraction/motility

Question 6

What can side chains of amino acids either be?

Answer 6

Either polar/hydrophobic

Question 7

Describe amino acids

Answer 7

Amino acids linked by peptide bonds, bond has trans and cis configuration
Most peptide bonds in trans

Question 8

Describe peptide bonds in terms of resonance isomers

Answer 8

Peptide bond has partial double character exists as 2 resonance isomers (there’s no rotation around the peptide bond)

Question 9

Describe primary structure of proteins

Answer 9

Unique, encoded by nucleotide sequence of DNA, read from amino to carboxyl terminus, alterations of single AA cause fatal diseases Eg SCA

Question 10

Describe secondary structures of proteins

Answer 10

Local folding of polypeptide chain, forming H-bonds btw C=O/N-H groups in backbone (chain without R groups - Main types of 2o - a-helix, b-sheet, b-turns, loops

Question 11

Describe a-helices

Answer 11

Most common, 3.6 residues per turn, H-bonds btw C=O group of residue n and N-H group of n+4, right-handed (clockwise), has dipole moment partial positive charge on N-terminus and partial neg charge at C-terminus
Side chains extend radially from a-helix core

Question 12

Describe b-pleated sheets

Answer 12

Peptide chains fully extended, pleated shaped as adjacent peptide groups can’t be coplanar, stabilized by H-bonds btw C=O/N-H groups of backbone, side chains extend from above/below

Question 13

Describe b-turns (reverse turns)

Answer 13

Reverse direction of polypeptide chain, turns C=O group of residue n is H-bonded to N-H group of residue n+3, most turns has at least 1 residue of glycine/proline

Question 14

Describe loops

Answer 14

Regions have many lengths, irregular shape, flexible, connect a-a-helices/b-b-sheets/a-b sheet

Question 15

Describe pi-helices

Answer 15

Very rare, occurs mostly at ends of a-helix, 4.4 residues per turn, H-bond btw residue n&n+5

Question 16

Describe supersecondary structures

Answer 16

Simple combos of secondary structure elements with specific geometric arrangement (motifs)

Question 17

Describe tertiary structure of proteins

Answer 17

Stabilised by bonds/interactions btw side chains > Vdw’s and hydrophobic interactions, H-bond, Ionic bond, Disulfide bonds btw Cys residues

Question 18

Describe quaternary structure of proteins

Answer 18

Spatial arrangement of subunits in oligomeric protein > Stabilised by same types of interactions btw side chains as tertiary structure (subunit can be identical/different)

Question 19

What are protein domains? Describe them

Answer 19

Single polypeptide chain folds into 2/more compact, spatially distinct units
Only 20% of eukaryotic proteins are single domain proteins

Question 20

What is the difference between domains and subunits?

Answer 20

A single polypeptide chain can form several domains but only 1 subunit

Question 21

Describe domain shuffling

Answer 21

Many domains appear in more than one protein (its thought many multidomain proteins have arisen during evolution by fusion of genes that encoded separate proteins in an ancestor)

Question 22

Describe the structural features of enzymes in terms of their general composition

Answer 22

Enzymes may need cofactor to function > Holoenzyme = Apoenzyme + Cofactor
Types of cofactors > Metal ions (Zn2+/Fe3+), Coenzymes (organic molecules), Prosthetic groups (organic molecules covalently bound to protein eg haem group in haemoglobin)

Question 23

Describe the active site if enzymes

Answer 23

Groove in protein containing residues that bind the substrate, perform catalytic reaction
Residues forming active site can be distant in sequence, complementarity btw active site and substrate eg size, shape, charge and hydrophobicity

Question 24

Describe other enzymes that have domains but differ in function

Answer 24

Phosphofructokinase 2 (PFK2) = Bifunctional enzyme with 2 domains > Kinase, Phosphatase

Question 25

Describe the diseases related to protein structure

Answer 25

Eg Gaucher disease - Most common lipid storage disease Caused by mutations in acid b-glucosidase gene that breaks down glucosylceramide into glucose and fat, ceramide Intracellular accumulation of glucosylceramide in spleen, liver, bone marrow

Question 26

Describe the acid-b-glucosidase structure

Answer 26

Known mutations in surface loop forms part of active site, enzymes reduces catalytic activity to stabilise conformation that limits access to active site

Question 27

Describe the affects of sickle cell anaemia

Answer 27

Affect millions, mostly sub-saharan africa Sickled cells cause blockages, deprives organs/tissues of O2. Normal RBC live ~120 days in blood, sickled cells die 10-20 days > Not enough RBC in blood hence anaemia

Question 28

Describe a mutation caused by protein structure

Answer 28

Sickle cell anaemia = Autosomal recessive disorder caused by single amino acid substitution in b-chain of haemoglobin (Glu > Val)

Question 29

Describe molecular mechanisms

Answer 29

Glu is hydrophilic but Val hydrophobic. Mutation creates hydrophobic patch on surface of protein that fits hydrophobic pocket created by Phe and Leu in deoxygenated form of another haemoglobin. Hydrophobic interactions cause haemoglobin to polymerise into fibres which cause RBC to become stiff and assume a sickle shape