1: Proteins I Flashcards

Question

What is the configuration of proline side chains and why?

Answer 1

Proline containing peptide bonds can be either cis or trans because their energies are more thermodynamically similar than in other resides Prolines ring structure causes steric clashes in both configurations resulting in no strong thermodynamic preference for one configuration over the other

Answer 2

Peptide units are planar Six atoms are in the same plane due to double bond characteristics of the peptide bond

Answer 3

Only the C-N bond is rigid The other bonds in the unit are free to rotate Which gives rise to two peptide bond configurations (cis/trans)

Answer 4

The polypeptide backbone is partially flexible The peptide bonds and the amide plane are rigid Amino acids can orient in different angles due to flexibility of the Cɑ-C and Cɑ-N bonds Only a certain combination of phi and psi are energetically favoured which is why the backbone is only partially flexible

Answer 5

The central carbon

Answer 6

ɸ The angle of rotation of the N-Cɑ bond

Answer 7

ψ The angle of rotation of the Cɑ-CO bond

Answer 8

Steric constraints: 1) The size of the side chain (R) 2) The planarity of the peptide unit

Answer 9

Beta-sheets Right-handed ɑ-helices common Left handed ɑ-helices very rare

Answer 10

Non-covalent interactions Weaker than covalent bonds But are vital to the stability of the 3D structure Hydrogen bonds, salt bridges, van der Waals

Answer 11

Occurs when a donor atom donates its covalently bonded hydrogen atom to an electronegative acceptor Strongest when the acceptor and donor lie in a straight line Hydrogen bonds are abundant in proteins and are crucial for folding and for the formation of secondary structure The hydrogen atom bonded to the N or O of an amino acid has a partial positive charge So can interact with partially negative charges on other atoms (e.g. carbonyl carbons)

Answer 12

Results from attractive forces between oppositely charged atoms Very important for quaternary structure At pH7, arginine and lysine are positively charged Glutamic acid and aspartic acid are negatively charged In acid or basic environments, electrostatic interactions can be disrupted, leading to protein unfolding due to salt bridges breaking

Answer 13

Electron cloud of non-polar atom will fluctuate to form temporary dipoles These can transiently induce oppositely polarised dipoles in neighbouring atoms This is a very weak interaction Occurs when two atoms are roughly 3-4Angstroms apart If they were too close they would repel

Answer 14

1) Spiral staircase 2) Each 360 turn of the spiral has 3.6 steps (amino acids) 3) Each amino acid ‘step’ adds 0.15nm in height 4) 0.54nm height per turn 5) Hydrogen bonds form between the C=O group of one residue and the N-H of the one four positions ahead 6) This helps to hold the spiral tightly together 7) Full helix length can vary from 4-40 amino acids 8) Often drawn as a helical wheel diagram

Answer 15

1) Hydrogen bonds occur on different but adjacent strands 2) They lie alongside one another, maximising number of hydrogen bonds 3) Multiple strands form beta-sheets containing up to 10-20 strands 4) Strands may be parallel or anti-parallel 5) Side chains of amino acids point above and below the sheet alternately The sheet is not planar, it is pleated 5) Adjacent antiparallel strands are connected by hairpin turns of variable length, which are stabilised by local hydrogen bonds, present at the surface of the molecule, are often rich in charged side chains, and often act as binding sites 6) Can form barrel structures

Answer 16

Folded Due to additional non-covalent bonding

Answer 17

In the universe (or any isolated system), the degree of disorder always increases over time

Answer 18

ΔG = ΔH - TΔS Where: ΔG is change in free energy ΔH is change in enthalpy T is temperature ΔS is change in entropy This equation enables us to determine if a reaction will occur spontaneously or not: If ΔG<0, it will If ΔG>0, it will not

Answer 19

The contribution of water molecules to the folding of a polypeptide chain Drives the formation of the hydrophobic core of protein Increases entropy of water molecules Promotes formation of tertiary structure

Answer 20

1) The polypeptide chain adopts a folded, compact structure under physiological conditions 2) Folded form is readily disrupted by temperature, pH, detergents, etc. 3) Proteins can be more gently unfolded by denaturants 4) Spontaneous refolding

Answer 21

Proteins that have the role of enhancing the rate at which other proteins fold Can be assisted in certain compartments of the cell or by other proteins that form disulfide bonds (or help isomerisation)

Answer 22

Infectious proteins that cause disease by triggering other proteins to misfold into an abnormal shape, altering their function

Answer 23

Metal ions: provide stabillity/catalytic activity Haem/chlorophyll prosthetic groups: perform specific tasks (e.g. selective oxygen binding) Cofactors: perform specific chemical reactions within enzymes active sites

Answer 24

Innate immunity Adaptive immunity

Answer 25

Rapid but non-specific Evolutionary-conserved E.g. macrophages, granulocytes, complement protein, natural killer cells, etc.

Answer 26

Slow but specific Immunological memory E.g. B-cells and T-cells Natural killer (cytotoxic) T-cells and γ-δ-T cells

Answer 27

Immunoglobulin = antibody Y-shaped globular proteins Made of two identical light chains and two identical heavy chains linked by disulfide bonds Hinge between the two arms allowing them to move to adjust to spacing of antigenic determinants Produced by B-cells In mammals there are five types (A,D,E,G, and M) Each one recognises a unique epitope or antigenic determinant They bind through complementary surfaces via great specificity

Answer 28

Any molecule that stimulates production of antibodies and is the target for an antibody Antibodies recognise and bind to invaders via their antigens But antibodies do not bind to host-cell antigens (except for in the case of autoimmune disease)

Answer 29

When the binding of an antibody to an antigen stimulates binding to C1 (the first protein in the complement complex) Which triggers an amplification cascade Thousands of molecules of membrane stack And they punch holes in pathogen membranes

Answer 30

Antibody-antigen complex Helps neutralise pathogens Marks antigens for destruction by phagocytes (opsonisation) Can activate complement

Answer 31

The process by which a pathogen is tagged (e.g. via antibodies or complement proteins) for destruction of pathogens

Answer 32

Binds to receptors on the outside of mast cells Triggers histamine release (e.g. in allergic reactions, such as hay fever)

Answer 33

A type of white blood cell found in tissues around the body Their function is to release histamine

Answer 34

1) A constant region (Fc) that is recognised by C1 and receptors 2) Variable domains (to recognise an almost infinite range of antigens) 3) Multivalency so it can form complexes 4) Flexibility so can adjust to different spacing of antigenic determinants

Answer 35

Hyper variable regions These are regions of high sequence variation in antibodies/immunoglobins Aside from these regions, there is little amino acid variability in the light and heavy chains HVRs can form loops to bind antigens Only found in the variable domain

Answer 36

Folded beta-sheet structure stabilised by disulphide bonds Conserved regions that maintain structure and function

Answer 37

Beta-sheet structure with loops at the antigen-binding site Contributes to diversity in antibody specificity HVRs form the antigen-binding site, where the variation allows recognition of a wide range of antigens

Answer 38

Variable domains Highly variable in sequence and form the antigen-binding site Variable domain allows antibodies to recognise a wide range of antigens while constant domains provide structural stability and are not involved in antigen binding

Answer 39

C-terminal residues of the heavy chain (337aa) and light chain (110aa) are identical across different IgGs These conserved regions are part of the constant domains and provide structural stability Variable regions (At the N-terminal) vary to allow specific antigen recognition

Answer 40

van der Waals Ionic interactions Burial of hydrophobic surfaces Hydrogen bonds

Answer 41

Burial of hydrophobic surfaces reduces exposure to water, which would destabilise the structure This encourages hydrophobic interactions between non-polar residues, which stabilises the protein’s core and increases structural strength by minimising the disruptive effect of water on protein folding

Answer 42

Crystal structure: Ab and lysozyme: 17 amino acids from the antibody make contact with 16 residues of the lysozyme The binding interface has a large combined surface area All six HVRs of the antibody contribute to the formation of the Ab-Ag complex, allowing for specific recognition and binding

Answer 43

Antibodies derived from a singular parent B-cell Produced in large quantities by fusion to tumour cells which can create hybrid cells to produce an indefinite amount of antibodies These antibodies have high specificity and affinity for their target antigen, making them useful in diagnostics