Ch 4

Question 1

What interactions stabilize structure?

Answer 1

Weak interactions
- hydrogen bonds
- hydrophobic effect
- ionic interactions

Question 2

Native protein

Answer 2

Proteins in any functional, folded, stable conformations

Question 3

What protein conformation has the lowest free energy (most stable conformation)?

Answer 3

The one with the maximum number of weak interactions

Question 4

Solvation layer

Answer 4

Highly structured shell of H2O around a hydrophobic molecule
- decreases when no polar groups cluster together
- decrease causes an increase in net etrophy

Question 5

Cation pi interaction

Answer 5

A noncovalent molecular interaction between the face of an electron rich pi system and an adjacent cation

Question 6

What amino acids contain polar functional groups and can undergo van der waals interactions?

Answer 6

M, W, Y, T

Question 7

Dihedral angle

Answer 7

The angle at the intersection of two planes

Question 8

Secondary structure

Answer 8

The spatial arrangement of the main chain atoms in a segment of a polypeptide chain without regard to the positioning of its side chain or its relationship to other segments

Question 9

Alpha helix

Answer 9

Simplest arrangement, maximum number of hydrogen bonds

Question 10

Each helical turn

Answer 10

3.6 residues, 5.4 A

Question 11

What destabilizes an alpha helix?

Answer 11

Charge, size, and shape of R chains

Question 12

Intrahelical hydrogen bonds

Answer 12

The hydrogen bonds formed within the alpha helix allows it to take form
Found between hydrogen atom attached to the electronegative nitrogen atom of the residue n and the carbonyl oxygen of residue n+4

Question 13

What amino acid has the greatest tendency to form alpha helices?

Answer 13

Alanine

Question 14

What amino acids infrequently occur in an alpha helix?

Answer 14

Proline and glycine

Question 15

What are the five constraints that affect the stability of an alpha helix?

Answer 15

1. The intrinsic propensity of an amino acid residue to form an alpha helix (n+4 hydrogen bonds)
2. The interactions between R groups, particularly those spaced three or four residues apart
3. The bulkiness of the adjacent R groups
4. The occurrence of pro and gly
5. The interactions between amino acid residues at the ends of the helical segments and the electric dipole inherent to the alpha helix

Question 16

Beta conformation

Answer 16

Backbone extends into a zigzag

Question 17

Beta strand

Answer 17

Single protein segment

Question 18

Beta sheet

Answer 18

Several strands in beta conformation side by side

Question 19

Beta turns

Answer 19

Connect ends of two adjacent segments of an antiparallel beta sheet

Question 20

What amino acids are likely to be found in a beta turn?

Answer 20

Proline and glycine

Question 21

Circular dichroism (CD) spectroscopy

Answer 21

Measures differences in the molar absorption of left handed vs right handed circularly polarized light

Question 22

Tertiary structure

Answer 22

Overall three dimensional arrangement of all the atoms in a protien

Question 23

Quaternary structure

Answer 23

Arrangement or 2+ separate polypeptide chains in three dimensional complexes

Question 24

Four major types of proteins groups based on polypeptide chains

Answer 24

1. Fibrous proteins = arranged in long strands or sheets
2. Globular proteins = folded into a spherical or globular shape
3. Membrane proteins = embedded in hydrophobic lipid
4. Intrinsically disordered proteins (IPDs) = lacking stable tertiary structure

Question 25

What are examples of fibrous proteins?

Answer 25

Alpha helix cross linked by disulfide bonds Collagen triple helix Beta conformation

Question 26

Alpha helix, cross linked by disulfide bonds (characteristics, example, amino acids)

Answer 26

Tough, insoluble protective structures of varying hardness and flexibility Alpha keratin of hair Hydrophobic residues: ala, Val, leu, met, phe

Question 27

Collagen triple helix (characteristics, example, amino acids)

Answer 27

High tensile strength, without stretch Collagen of tendons, bone matrix Left handed, repeated tripeptide unit Gly-Y-X where X is often pro and Y is often 4-Hyp

Question 28

Beta conformation (characteristics, example, amino acids)

Answer 28

Soft, flexible filaments Silk Ala and gly

Question 29

Globular proteins

Answer 29

Fold back on each other More compact than fibrous proteins Can be composed of a mixture of alpha helices and beta conformations Ex: enzymes, transport proteins, immunoglobulins

Question 30

Structural motif

Answer 30

Recognize folding pattern involving 2+ elements of secondary structures and the connections

Question 31

Protein folding rules

Answer 31

- burial of hydrophobic R groups requires 2+ layers of secondary structure - alpha helices and beta sheets are found in different layers - adjacent amino acid segments are usually stacked adjacent - the beta conformation is most stable with right handed connections

Question 32

Alpha/beta barrel

Answer 32

Series of beta, alpha, beta loops arranged such that the beta strands form a barrel

Question 33

Domain

Answer 33

Part of a polypeptide chain that is independently stable or could undergo movements as a single entity

Question 34

Membrane proteins

Answer 34

Found anchored or within cell membranes Non polar (hydrophobic) amino acids associated with with the lipid bilayer inside the membrane Polar (hydrophilic) amino acids are located internally and face aqueous solutions

Question 35

Intrinsically disordered proteins (IDPs)

Answer 35

- lack definable structure - often lack a hydrophobic core - high densities of charged residues (lys, arg, glu) and pro - higher probability of being posttranslationally modified (PTMs) - facilitates a protein to interact with multiple binding partners

Question 36

Proteostatsis

Answer 36

Continual maintenance of the active set of cellular proteins required under a given set of conditions

Question 37

Proteasis pathway

Answer 37

1. Proteins synthesized on ribosome 2. Various pathways contribute to folding 3. Proteins that are inversely unfolded are subject to sequestration and degradation by additional pathways

Question 38

Chaperone proteins

Answer 38

Proteins that interact with partially folded or improperly folded proteins and prevent aggregation

Question 39

Chaperonins

Answer 39

Required for the folding of proteins that do not fold spontaneously

Question 40

Amyloid fiber or fibrils

Answer 40

Protein secreted in a misfolded state/protein aggregates that form from insoluble extracellular fibers and are resistant to degredation

Question 41

Alzheimer’s disease

Answer 41

Associated with extracellular amyloid deposition by neurons, involving the amyloid beta peptide

Question 42

Alzheimer’s disease

Answer 42

Associated with extracellular amyloid deposition by neurons, involving the amyloid beta peptide

Question 43

Parkinson’s disease

Answer 43

Misfolded from alpha synuclein aggregates into spherical filamentous masses called lewy bodies

Question 44

Huntington’s disease

Answer 44

Involves the intracellular aggregation of Huntington, a protein with long polyglutamine repeat

Question 45

ALS

Answer 45

Intracellular stress, RNA metabolisms, mitochondrial defects

Question 46

Cystic fibrosis (CF)

Answer 46

Caused by defects in the membrane bound protein cystic fibrosis transmembrane conductance regulator (CFTR)

Question 47

Prion protein (PrP)

Answer 47

Misfolded brain protein

Question 48

X-ray crystallography

Answer 48

Pattern of diffracted x-rays is collected and an image is reconstructed by mathematical techniques Shows final conformation High resolution because object is not moving

Question 49

NMR

Answer 49

Carried out on molecules in solution and gives better understanding of how it functions at physiological pH Measures resonance of atoms Allows you to ID proteins Shows protein folding, conformational change and interactions with another molecule

Question 50

Cryo-EM

Answer 50

Sample of the structure of interest is quick frozen in ice and kept frozen while being observed in two dimensions with EM Shows structure of large, dynamic macromolecules and integral membrane proteins Won’t be precise because object is moving Low to medium reabsorption

Question 51

CD spectroscopy

Answer 51

Used for secondary structures Gives the fraction of protein made of alpha helices, b conformations and unstructured regions Measures polar absorption of circularly polarized light by the peptide bonds when folded