Tertiary and Quaternary Protein Structures (Zhao L3)

Question 0

What are some characteristics of the fibrous tert. protein structue?

Answer 0

Insoluble (typically)
Made from a single secondary structure
Structural or Protective function

Question 1

What are the two protein tertiary structures?

Answer 1

1. Fibrous

2. Globular

Question 2

What are some characteristics of the globular tert. protein structure?

Answer 2

Water soluble OR
Lipid soluble (membrane proteins)
Generally made up of many secondary structures

Question 3

Why are loops and turns important in tert. protein structure?

Answer 3

Allow for more diverse 3D structure connecting the secondary (beta sheet, alpha helix) structures
Can play a functional role in the molecule

Question 4

Which two amino acids are very common in loops and turns?

Answer 4

1. Glycine - small = flexibility

2. Proline - ring bond to backbone N makes it disrupt helices and sheets.

Question 5

How are loops important in antibodies?

Answer 5

The variable region of an antibody have loops with residues that recognize antigens.

Question 6

What is a “motif” in protein structure?

Answer 6

A common arrangement of secondary structures that occurs similarly in different proteins and has similar functions across different proteins.

Question 7

What is a “domain” in regards to protein structure?

Answer 7

A stable globular unit in a protein with a more-or-less independent function.

e.g. binding domain vs. activator/repressor domain

Question 8

Suppose a fibrous protein contains only alpha helices connected by S-S bridges. What is its likely function(s) and location(s)?

Answer 8

It is tough, rigid, hard and likely
found in nails or horns
alpha-Keratin

Question 9

Suppose a fibrous protein contains mostly cross-linked triple helixes with a flexible (HyPro) linker. What is its likely function(s) and location(s)?

Answer 9

High tensile strength, not stretchy
Tendons, cartilage
Found in Collagen

Question 10

Suppose a fibrous protein contains mostly non-covalently held beta sheets (van der Waals interactions). What is its likely functin(s) and location(s)?

Answer 10

Soft, flexible, non-stretchy
Egg sac, nest, web.
Silk

Question 11

Give some examples of globular proteins

Answer 11

myoglobin, ferritin
hemoglobin, serotonin transporter
antibodies, cytokines
actin, myosin
chymotrypsin, lysozyme

Question 12

Ligands bind to binding proteins via ______ forces enabling the interaction to be ________.

Answer 12

non-covalent

transient

Question 13

Define K_d for a ligand binding to a protein.

Answer 13

The concentration where half the available ligand is bound to the protein.

Question 14

Describe the lock and key model for ligand binding.

Answer 14

High specificity enabled by size, shape, charge and hydro-phobic/phillic character of the ligand and binding protein.

Question 15

Describe Induce Fit for ligand binding.

Answer 15

Conformational changes to the ligand and binding protein upon binding to achieve a better fit.

Question 16

What does Myoglobin do?

Answer 16

Stores Oxygen for later use

Question 17

Where / How does myoglobin bind oxygen?

Answer 17

“buried” deep in the protein. Heme ring reversibly binds oxygen.

Question 18

Heme binds CO ___________ than O2.

Answer 18

20,000 times better

Question 19

How does hemoglobin optimize O2 binding, transport and delivery?

Answer 19

Multiple binding sites interact with each other. Once the first heme group binds, others have higher affinity for O2. (T & R states)

Question 20

What is the T state of hemoglobin and what tissue is it likely found in?

Answer 20

T = tense. low O2 affinity

found in Tissues to release O2 for use

Question 21

What is the R state of hemoglobin and what tissue type is it usually found in?

Answer 21

R = relaxed
high O2 affinity
found in the lungs for better O2 binding

Question 22

What is the Bhor effect in regards to hemoglobin O2 affinity.

Answer 22

Reciprocal relationship of hemoglobin affinity for O2 and CO2 dep. on pH

Low H+, CO2 affinity (High pH) –> high O2 affinity
High H+, CO2 affinity (Low pH) —> low O2 affinity

Question 23

What are some methods for determining protein structure?

Answer 23

1. X-ray crystallography

2. NMR (yay!)

Question 24

Pros and Cons of X-Ray crystallography?

Answer 24

Pro: no size limit
Con: crystallization is rate limiting step & unpredictable

Question 25

Pros and Cons of NMR?

Answer 25

Pro: No need to crystalize
Con: Need very concentrated sample
difficult for large proteins (>30kD)

Question 26

Why is it helpful to know a protein’s structure?

Answer 26

Helps to understand function

Designing Drugs

Question 27

What class of drugs can be used to inhibit many protein-protein interactions?

Answer 27

Antibody. Will bind to interfere with protein-protein binding.