Biochem Lecture 4

Question 1

Explain what tertiary structure is

Answer 1

Tertiary structure is the 3D structure of a polypeptide due to the condensation of secondary elements

Tertiary structures are stabilized by weak interactions

Very high density, but cavities exist

Covalent bonds, metal ion coordination and post-translational modifications can add stability to tertiary structure

Question 2

What is a domain?

What is essential for a domain’s stability?

Answer 2

A domain is a compact unit of protein structure that is usually capable of folding stably on its own

Domains have hydrophobic cores. These hydrophobic cores are essential for the stability of domains.

Question 3

Define structural motif

Define domain fold

Answer 3

Structural motif consists of small local arrangement of secondary structural elements which coalesce to form domains

Domain fold: combination of motifs

Question 4

Explain what an helix turn helix is

Answer 4

Two helices lying antiparrallel connected by a turn/loop

Calmodulin is an example of this (it contains multiple alpha loop alpha)

Question 5

Define the following terms: class, fold, family

Answer 5

Class: determined by predominant secondary structures

Fold: determined by arrangements of secondary structures within a domain

Family: sequence idenity

Question 6

What is a superfold?

Answer 6

Superfolds are folds of similar structure that are in proteins of unrelated functions.

Question 7

Explain the following about alpha helices (the secondary structure)

What is the pitch

How many residues per turn

What is bonded to what?

Describe confirmation/shape

Relationship btw dipole strength and length

Answer 7

So the pitch is 5.4 A, because the structure repeats itself every 5.4 angstroms

There are 3.6 AA residues per turn

(Rise per residue is pitch/residues per turn) = 1.5 A

Every main C=O and N-H are hydrogen bonded to a peptide bond 4 residues away

Peptide bonds are parallel to the helical axis

R groups point outwards and towards the N terminus

Strength of dipole increases with length

Question 8

Two common motifs for alpha domains are the _________ & _________

Answer 8

Two common motifs for alpha domains are the 4 helix bundle and the globin fold.

Question 9

Explain the all beta topology. What is there preferred arrangement? What does that mean for polar vs hydrophobic residues?

Answer 9

Most or entirely beta sheets means they will be antiparallel arrangement. Many of these anti-parallel domains consists of two beta sheets packed against each other, with hydrophobic side chains in the inside.

Sequence of alternating hydrophobic and polar residues

Question 10

How can you identity an orthagonal beta sandwich?

Answer 10

Angle between sheets has a right handed twist of 90 degrees. The strands at one corner or two diagonally opposite corners bend at a 90 degree angle.

Question 11

Antiparallel beta strand can form ____ and ____.

Answer 11

Sandwiches and barrels

Question 12

Explain what a greek key is

Answer 12

A greek key has up-down beta strands connected by hairpins. The first structure is connected to the fourth.

“three up and down beta strands connected by hairpins”

Question 13

Two major families in alpha/beta domains are?

Answer 13

Alpha/beta: twists and barrels

Question 14

Give definitions of the following:

Beta-barrel

Beta sandwich

Jelly roll

Answer 14

Beta-barrel: single beta sheets forms cylindrical structure in which all strands are H bonded with one another

Beta sandwich: formed of two antiparallel beta sheets packed face to face

jelly roll is an extra swirl on a greek key

Question 15

Explain the alpha/beta domain

Answer 15

All of the beta’s will be parrallel with each other

All of the alphas are parrallel with each other

Beta and alpha are antiparralel to each other

Form twists and folds

Question 16

The rossman fold

Answer 16

beta strands are parrallel and H bonded to each other

Helices are parrallel and H bonded to each other

Helices are antiparrel to beta strands

Rossman fold is beta alpha beta alpha etc

Question 17

Alpha + beta domains

Answer 17

do NOT exhibit wound alpha beta topology

Independent helical motifs packed against a beta sheet

Question 18

Explain quaternary structure

Define “oligomer”

Answer 18

The NONCOVALENT arrangement of peptide chains in a multiunit protein

Oligomer: protein assembles composed of more than one polypeptide chain

Question 19

What are the four types of fibrous proteins?

List the differences between globulin and fibrous proteins

Answer 19

Fibrous proteins: collagen, elastin, alpha keratin, tropomyosin

Fibrous proteins:

• contain larger amounts of regular secondary structure
• have extended clindrical/rod shape
• VERY LOW solubility
• play structural rather than dynamic role

Question 20

Collagen is rich in which AA’s

What does the enzymatic conversion of proline to 4-hydroxyproline require?

Collagens are glycoproteins with the carbohydrate linked to the 5 hydroxylysine via______.

Answer 20

Collagen is rich in glycine, proline and 4-hydroxyproline and 5-hydroxylysine

Enzymatic concersion of proline to 4hproline requires Vitamin C, so in scurvy there is reduced collagen synthesis

via O-glycosidic linkages

Question 21

Primary structure of Collagen

Answer 21

Basic unit of collagen is a polypeptide with the repeating sequence of :

(Gly-X-Y)n

where X is often proline and Y is often hydroxyproline

THREE residues repeated over and over starting with glycine

Question 22

Three chains of a collagen molecule are wound about each other to form a ______.

This structure (superhelix) forms because_____.

The glycines in each chain are aligned along one side of the helix forming a _____.

The glycine edges associate _____ to form the superhelix structure.

Answer 22

Three chains of collagen are wound to create superhelix.

This superhelix forms because glycines have low steric bulk.

The glycines aligned along the side to form APOLAR edge.

The glycine edges associate noncovalently.

Question 23

Covalent crosslinks in are formed in collagen via ______.

Formations of those _____ is catalyzed by?

Answer 23

Covalent crosslinkes are formed in collagen via allysine intermediates.

Formations of those allysines are catalyzed by lysyl amino oxidase.

NOTE: This covalent crosslinking within a strand via reaction of lysine residues to form aldol cross-links

THIS IS NOT QUATERNARY structure because it is now covalent.

Question 24

Elastin is another fibrous protein with _____.

It lacks a ________.

Answer 24

Elastin is another fibrous protein with allysine generated crosslinking.

Lacks regular secondary structure but does form a coil

FORMS extensive crosslink structures via allysine

Question 25

Alpha keratin and tropomyosin sequence show a tandem repitition of 7 residue segments:

a-b-c-d-e-f-g

Which are hydrophbic and which are polar?

Answer 25

a and d (1 and 4) have hydrophobic side chains

e and g (5 and 7) have polar side chains

Apolar residues form an edge

Question 26

Apolipoproteins have a high ____ content when associated with lipid.

Why is that?

The helical regions have _________ properties.

Answer 26

Apolipoproteins have a high alpha helical content when associated with lipid. This is because every third or fourth residue is CHARGED and forms a POLAR edge that associate with water.

Helical regions have ampipathic properties.