Lecture 9 - Examples of Protein Functions

Question 1

what are 3 main protein functions?

Answer 1

1. myoglobin + hemoglobin
2. muscle contraction: actin/myosin
3. immunoglobulins (antibodies)

Question 2

what is myoglobin?

Answer 2

O2 binding protein

Question 3

how many residues in myoglobin?

Answer 3

153

Question 4

how many helices in myoglobin?

Answer 4

8 helices, A through H

Question 5

what is the functional part of myoglobin?

Answer 5

“heme” which contains fe(II)

Question 6

what happens when Fe(II) is oxidized

Answer 6

Fe(III) is inactive

metmyoglobin

Question 7

what is the fused ring of myoglobin?

Answer 7

porphyrin molecule

Question 8

how is the underside of the porphyrin coordinated?

Answer 8

by His93

Question 9

what is the porphyrin held into place by?

Answer 9

a number of hydrophobic residues

Question 10

what is O2 stabilized by when bound?

Answer 10

His64

Question 11

what does myoglobin facilitate?

Answer 11

O2 diffusion in a muscle

Question 12

What does O2 binding to myoglobin show?

Answer 12

typical “saturation” behavior

Question 13

What is the equilibrium between free and bound O2?

Answer 13

MbO2 <> Mb + O2

Question 14

What is free O2 in muscle measured by?

Answer 14

partial pressure PO2

Question 15

What is PO2?

Answer 15

free O2 in muscle

Question 16

What is YO2?

Answer 16

fraction of Mb that has a bound O2

Question 17

what is hemoglobin?

Answer 17

a transport protein

Question 18

where does hemoglobin transport O2?

Answer 18

in the circulatory system

Question 19

what is hemoglobin responsible for?

Answer 19

the red color of erythrocytes

Question 20

What is mammalian Hb?

Answer 20

• a tetramer

- consists of 2 identical alpha subunits (pink) and 2 identical beta subunits (yellow)

Question 21

Hb can bind up to _____ O2

Answer 21

four

Question 22

What happens when Hb binds O2?

Answer 22

• a major shift occurs in its quaternary structure

- interface between the 2 beta subunits closer together

Question 23

How does hemoglobin bind O2?

Answer 23

cooperatively

Question 24

what type of shape does the O2 binding curve on Hb have?

Answer 24

sigmoidal shape

Question 25

What does the s-shaped binding curve signal?

Answer 25

cooperativity

Question 26

When going toward high PO2, after one O2 binds, what happens to the next?

Answer 26

it binds more easily

Question 27

What happens when going toward a low PO2, after one O2 unloads?

Answer 27

the next one unloads more easily

Question 28

How does the pattern of PO2 and O2 binding and unloading affect Hb?

Answer 28

- helps Hb deliver more O2 to tissues | - compared against Mg

Question 29

What does the Hill Coefficient describe?

Answer 29

cooperativity Hb(O2)n <> Hb + n O2

Question 30

For the Hill Coefficient,, what does n>1 mean? n<1?

Answer 30

n>1 positive cooperativity n<1 negative cooperativity

Question 31

What is the hill plot?

Answer 31

-the rearrangement of the Hill equation to yield a straight-line plot

Question 32

Do hemoglobin T and R conformations have the same affinity for O2?

Answer 32

-different affinity

Question 33

T vs. R

Answer 33

``` T = deoxy form (tense) R = oxy form (relaxed) ```

Question 34

What is the effect of the hme and the F helix during the T->R transition?

Answer 34

- makes O2 bind more strongly in R | - disrupts series of ion pairs + H bonds between alpha and beta subunits

Question 35

What happens when the ion pairs and H bonds are disrupted?

Answer 35

- modifies pKa of residues | - alters the O2 binding as a function of pH

Question 36

What is the Bohr effect?

Answer 36

-changes the loading of Hb as a function of pH

Question 37

What is O2 binding to Hb accompanied by?

Answer 37

-the release of ~0.6 H+

Question 38

What do capillaries have?

Answer 38

CO2

Question 39

What happens when CO2 is dissolved in blood?

Answer 39

-makes bicarbonate HCO3-

Question 40

what acceleartse the formation of bicarbonate HCO3-?

Answer 40

-enzyme carbonic anhydrase

Question 41

When is blood more acidic?

Answer 41

-PCO2 is high

Question 42

Where is PCO2 high?

Answer 42

-in the capillaries of the muscle

Question 43

Where is PO2 low?

Answer 43

in the capillaries in the muscle

Question 44

what happens to O2 in the muscle tissues?

Answer 44

- O2 unbinds - Hb takes up H+ - causes CO2 removal

Question 45

Where is PO2 high?

Answer 45

in the lungs

Question 46

What happens to O2 int he lungs?

Answer 46

- O2 binds - Hb releases H+ - releases CO2 into lungs to be expelled when exhaling

Question 47

what are allosteric interactions?

Answer 47

- enable protein subunits to work together | - binding of a ligand at one site affects the binding of another ligand at another site

Question 48

what are two models of allosteric effects?

Answer 48

1. sequential | 2. symmetry

Question 49

what is the sequential model of allosteric binding?

Answer 49

-assumes binding causes further affinity enhancement

Question 50

what is the symmetry model of allosteric binding?

Answer 50

-assumes an equilibrium exists between low and high affinity states