Signal Transduction

Question 1

Post-Translational Modification

Answer 1

Most important in multicellular eukaryotes
Phosphorylation
Acetylation
Methylation
Ubiquitnination
Effects: change surface properties of protein

Question 2

Why Phosphate as PTM?

Answer 2

Phosphate is big and has highly [ ] negative charge
ATP readily acts as phosphate donor
Reactions are thermo favorable but kinetcally slow and thus can be enzymatically controlled

Question 3

Which AA get phosphorylated

Answer 3

Serine and Threonine (both have free OH) done by same/similar enzyme
Tyrosine only found in multicellular animals

Question 4

Assembly and Disassembly of Signaling Complexes

Answer 4

Alter subecellular localization of proteins
Associate enzymes with their substrate
Assemble complex multifunctional strucutres that can integrate and coordinate activites

Question 5

Writer vs. Eraser

Answer 5

Writer puts something on protein, eraser removes it.

i.e. kinase = writer, phosphatase = eraser

Question 6

Kd

Answer 6

Dissociation constant
At equilibrium kon [A][B] = koff [AB]
Kd = Koff / Kon = [A][B] / [AB]
Kd has units of concentration

Question 7

What does Kd mean?

Answer 7

Kd is [ ] of B at which half of A is free and half is bound to B
If B > Kd then most of A is bound to B
If B < Kd then most of A is free

Question 8

Fractional Occupancy

Answer 8

F.O = [B] / (Kd + [B])

Question 9

Which has the greater affinity for substrate?

Kd1 = 10^-15 or Kd2 = 10^-4

Answer 9

Kd1 => less substrate is free and majority is bound to enzyme
NB: Kd = Koff / Kon = [A]*[B] / [AB]

Question 10

Affinity

Answer 10

Measure of how likely two components are to bind to each other at a given [ ]

Question 11

Specifity

Answer 11

Measure of the affinity of two components compared to the affinity of other possible binding partners

Question 12

Regulated Subcellular Localization of Signaling Proteins

Answer 12

Substrates are not uniformly distributed in the cell. The activity of a protein will depend on the local [ ] of these partners
Regulated by transcription and membrane localization

Question 13

JAK / STATS is an example of?

Answer 13

Nuclear Localization
Prolactin binds to receptor. Activated receptor activates JAK protein via phosphorylation. JAK protein causes STAT to dimerize becoming active.
Active STAT acts as transcription factor.

Question 14

Regulation of protein conformation in signaling

Answer 14

Same protein can exist in multiple 3D conformations, which have different activities
i.e. Calmodulin, Hemoglobin

Question 15

Catalytic Properties of Signaling Proteins

Answer 15

Potential for large signal amplification action at a distance
i.e. Caspase cascade

Question 16

Small molecule Second messenger

Answer 16

Signal leads to production of highly diffusible product that can regulate downstream effectors
i.e. cAMP, Ca2+, IP3 and DAG
NB: Secondary messengers are small

Question 17

Modular Architecture

Answer 17

Conserved domains of proteins are rearranged to create complex proteins

Question 18

Domain

Answer 18

A compact, independently folding unit of protein structure.

i.e. Rho GEF

Question 19

Modular Signaling Proteins Scaffold

Answer 19

These types of proteins allow for binding of specific substrate to the specific enzyme. Scaffolding protein increase specificity.

Question 20

G Proteins

Answer 20

Have slow intrinsic GTPase activity
Normally only active in GTP state
Release of GDP (Koff) is very slow
GEF (Guanine Exchange Factor) promotes activiation
GAP (GTPase Activator Protein) promotes turning off G-Protein

Question 21

G-Protein Coupled Receptors

Answer 21

Can act as GEFs

Question 22

Getting Information Across the membrane

Answer 22

Use readily diffusable proteins
i.e. NO or Hormones

Bind to receptors to relay message
i.e. G proteins
Tyrosine Kinase Receptors

Gated Ion Channels
i.e. Ca++ ion channel with Vassopressin