Lippincott CH2: Structure of Proteins

Question 1

How are peptide bonds formed?

Answer 1

Amide linkage between alpha-carboxyl group of one amino acid and alpha-amino group of another.

Question 2

What is a residue?

Answer 2

a single amino acid in a polypeptide chain

Question 3

How is a polypeptide named?

Answer 3

from N- to C- terminal. suffixes are changed to -yl with the exception of the C-terminal amino acid.
e.g. valylglycylleucine

Question 4

Which bonds in a polypeptide can freely rotate and which can’t?

Answer 4

The peptide bond cannot rotate because it is shorter than a single bond and is rigid & planar.
Bonds between the alpha carbons and the alpha amino or alpha carboxyl groups can freely rotate (R group can rotate).

Question 5

In what configuration is the peptide bond?

Answer 5

Almost always a trans bond. Due to steric interference of R groups when in cis position.

Question 6

What type of enzyme cleaves peptide bonds?

Answer 6

peptidases (proteases)

e. g. Exopeptidases: cut at ends of proteins. Classified into aminopeptidases and carboxypeptidases.
e. g. Endopeptidases cut within a protein

Question 7

How many amino acids are in each turn of an alpha-helix?

Answer 7

3.6 amino acids

Question 8

What configuration are alpha helices in?

Answer 8

Right-handed spiral

Question 9

Which amino acid disrupts an alpha helix?

Answer 9

proline, due to its secondary amino group - not geometrically compatible with right-handed spiral and causes a kink in thechain.

e. g. glutamate, asparate, histidine, lysine, and arginine also disrupt the helix by forming ionic bonds or by electrostatically repelling each other.
e. g. bulky amino acids that branch at the beta-carbon can interfere with formation of the alpha helix, in large numbers

Question 10

How do hydrogen bonds in alpha helices and beta sheets differ?

Answer 10

amino acid residues in alpha helices space three/four resides apart participate in hydrogen bonding for stabilization of the structure
in beta sheets, all of the peptide bond components are involved in hydrogen bonding

in alpha helices, hydrogen bonds are parallel to the spiral.
in beta sheets, hydrogen bonds are perpendicular to the polypeptide backbone

Question 11

what are the 2 conformations of the beta sheet?

Answer 11

parallel & antiparallel based on N terminal to C terminal alignment

Question 12

Discuss interchain vs intrachain bonds in the beta-pleated sheet.

Answer 12

interchain bonds are between 2 separate polypeptides.

intrachain bonds occur when a single polypeptide folds back and bonds with itself to form the beta-pleated sheet.

Question 13

to which structure are twisted beta-sheets important?

Answer 13

globular proteins, specifically the core of globular proteins.
***beta sheets always have a right-handed curl, or twist, when viewed along the polypeptide backbone in globular proteins

Question 14

define beta-bends

Answer 14

Beta bends rever the direction of a polypeptide chain, helping it form a compact, globular shape. usually found on surface of protein molecules and often include charged residues.

• ** given this name because they often connect successive strands of ANTIPARALLEL beta-sheets.
• *generally composed of 4 amino acids, one of which may be proline (for kink) and glycine (smallest R group)
• beta bends are stabilized by hydrogen & ionic bonds

Question 15

list the non-repetitive secondary structures

Answer 15

• random coil

- loop

Question 16

list common motifs involving alpha helices and beta sheets

Answer 16

• alpha alpha (helix, loop, helix)
• beta alpha beta
• beta meander
• beta barrel

Question 17

define domain.

Answer 17

a domain is the fundamental functional and three-dimensional structural units of polypeptides. (tertiary structure)

Question 18

How many domains does a 100 amino acid chain form?

Answer 18

1. Polypeptide chains that are greater than 200 amino acids in length generally consist of two or more domains.
   * **number isn’t significant. the point of this is to know that polypeptide chains can form multiple domains

Question 19

What structure drives the folding formation of tertiary structures?

Answer 19

interactions between amino acid side chains

Question 20

list the interactions that stabilize tertiary structures of globular proteins

Answer 20

• disulfide bonds
• hydrophobic interaction (hydrophobic effect)
• hydrogen bonds
• ionic bonds

Question 21

What amino acid forms a disulfide bond? What type of bond is this?

Answer 21

sulfhydryl groups (-SH) of 2 cysteine residues, covalent bond

Question 22

trace formation of a protein monomer from translation in the cell

Answer 22

1. translation results in a polypeptide (primary structure)
2. formation of secondary structures (via hydrophobic effect)
3. formation of domans (tertiary)
4. formation of final protein monomer (folding on itself)

Question 23

Why do most polypeptides, after they are denatured, not refold when returned to favorable environmental conditions.

Answer 23

most polypeptide folding is facilitated by a special group of proteins: chaperones (& they use ATP)

Question 24

How do molecular chaperones work?

Answer 24

charperones facilitate correct protein folding by binding to and stabilizing exposed, aggregations-prone hydrophobic regions in nascent/denatured polypeptides, preventing premature folding

Question 25

list interactions between subunits of a quarternary structure

Answer 25

covalent interactions e.g.

• hydrogen bonds
• ionic bonds
• hydrophobic interactions

Question 26

define isoform

Answer 26

isoforms are proteins that perform the same function but have different primary structures
(aka isozymes, if enzyme)

Question 27

define amyloid

Answer 27

insoluble, spontaneously aggregrating proteins, usually resulting from misfolded proteins or abnormal proteolytic cleavage of normal proteins

Question 28

list amyloid diseases

Answer 28

• Parkinson
• Huntington
• Alzheimer

Question 29

What amyloid causes Alzheimer’s?

Answer 29

amyloid beta (AB)
****second factor involved in the development of Alzheimer's is accumulation of neurofibrillary tangles inside neurons; abnormal form of tau protein

Question 30

What kind of disease is Creutzfeldt-Jakob disease?

What causes this disease?

Answer 30

• Prion disease. Transissible Spongiform Encephalopathy (TSE). Found in sheep (scrapie) & cows (mad cow).
• The prion protein (PrP), called PrP^c in humans (c=cellular) is present in normal mammalian brains on surface of neurons and glial cells and serves as host protein. Infectious protein is designated PrP^sc (sc-scrapie). The infective agent is an altered version of the normal protein, which acts as a template for converting the normal protein to the pathogenic conformation - a number of alpha-helices are replaced by beta-sheets. This results in an exponential increase of the infectious form.

Question 31

Why is the interchain hydrogen bond a unique characteristic to the beta-sheet and not the alpha-helix?

Answer 31

Interchain hydrogen bonds occur between 2 polypeptides. An alpha helix & some beta-sheets are formed by a single polypeptide - thus it has intrachain hydrogen bonding.