Midterm 3 (Chapters 9-15)

Question 1

what is plectin

Answer 1

a bridge made of an elongated dimeric protein that connects cytoskeletal filaments

Question 2

what are the 3 major components of the nuclear envelope

Answer 2

nuclear pores, nuclear membranes, nuclear lamina

Question 3

how does the nuclear envelope dissolute at the end of prophase

Answer 3

phosphorylation of human lamin causes de-polymerization and subsequent disassembly of the lamina

Question 4

describe the structure of actin

Answer 4

F-actin: filamentous
G-actin: Globular, (-) end has exposed ATP binding cleft which binds to the (+) end in a filament, (+) end has the C and N terminus, is where the (-) end of G actin binds

Question 5

cofilin

Answer 5

binds ADP actin and severs filaments
promoting depolymerization

Question 6

profilin

Answer 6

• functions as an adenine exchange factor
• Binds to ADP actin, changing the
  conformation and allowing binding of ATP
• Can bind to the(+)end of a growing filament
• Binding results in dissociation of profilin

Question 7

thymosin

Answer 7

• sequesters G- actin preventing
  polymerization
• Displacement of thymosin allows binding
  of G-actin to the plus end

Question 7

thymosin

Answer 7

• sequesters G- actin preventing
  polymerization
• Displacement of thymosin allows binding
  of G-actin to the plus end

Question 8

F actin cycle

Answer 8

a small piece of F-actin detaches from the filament during the cofilin cycle and becomes globular ADP actin, after the profilin cycle this becomes ATP-actin since profilin binds to it. then the thymosin cycle thymosin binds once it detaches the actin binds to the + end of the F-actin

Question 9

capping plus end vs capping minus end:

Answer 9

plus: prevents the filament from growing
minus: prevents the loss of subunits

Question 10

arp2/3 complex

Answer 10

(actin related proteins) nucleate new branches off the sides of existing filaments. minus end attaches to filament

Question 11

sarcomere

Answer 11

myosin overlaps, basic unit of muscle contraction, composed of actin and myosin

Question 12

capZ

Answer 12

maintains attachment and caps
actin at plus end

Question 13

Troponin complex

Answer 13

binds to tropomyosin Both have regulatory roles in contraction

Question 14

Tropomodulin

Answer 14

caps the (-) end

Question 15

Myomesin

Answer 15

bundles the myosin
filaments

Question 16

Nebulin

Answer 16

consists of repeating actin
binding motifs, dictates the length of an
actin (thin) filament and binds filament
to Z line

Question 17

Titin

Answer 17

extends through the myosin
(thick) filament and attaches to the Z
disk – helps to prevent tearing of
muscle

Question 18

extracellular signal to cellular response pathway

Answer 18

1. synthesis of the signalling molecule
2. release of the signalling molecule via exocytosis
3. transit of signalling molecule to the target cell
4. binding of signalling molecule (ligand) to a protein receptor on the target cell
5. binding of ligand to receptor results in a conformational change of the receptor
6. receptor initiates one or more intracellular pathways
7. deactivation of the receptor
8. removal of the ligand

Question 19

describe 4 types of intracellular signalling

Answer 19

1. endocrine: messenger molecules reach their target cells through the bloodstream (insulin)
2. paracrine: messenger molecules travel short distances through extracellular space (neurotransmitters)
3. autocrine: cell has receptors on its surface that respond to the messenger (t-cells during immune response)
4. juxtacrine: short range but requires physical contact between sending and receiving cells (antigen presentation)

Question 20

2 types of receptors

Answer 20

1. cell surface receptors
2. intracellular receptors

Question 21

what is a second messenger

Answer 21

small substances that activate or inactivate specific proteins. increases or decreases in concentration in response to the first messenger (can be anywhere along the cascade). bind to other proteins to modify their activity

Question 22

phosporylation

Answer 22

the addition of phosphate groups to hydroxyl groups on serine, theonine and tyrosine. part of almost all signalling pathways. changes a protein charge and generally conformation. carried on by kinases, dephosphorylation carried out by phosphatases

Question 23

GTPase superfamily

Answer 23

enzymes that hydrolyze GTP to GDP

Question 24

molecular switches

Answer 24

active (on): GTPase, bound GTP that modulates the activity of specific target proteins which they bind. GAPS help activate inactive (off): GDP is attached. GEFs enter and release GDP for GTP

Question 25

G protein coupled receptor (GRK)

Answer 25

GRK phosphorylation sites for receptor downregulation. sites of phosphorylation in the cytosol so OOC- can bind

Question 26

what does active G protein do

Answer 26

binds to an effector protein

Question 27

G proteins activate adenylyl cyclase

Answer 27

GTP subunit binds to activated enzymes. converts ATP to cyclic AMP, small messenger molecules diffuse to act on intracellular proteins (second messenger, cyclic AMP) interacts with protein kinase A

Question 28

since kinase A phosphorylates so many things,

Answer 28

it is often sequestered in certain parts of the cell to keep the signal targeted (AKAPs - A Kinase anchored protein)

Question 29

signal transduction by RTKs is usually terminated by:

Answer 29

internalization of the receptor primarily through clathrin-mediated endocytosis

Question 30

gain of function mutation

Answer 30

proto-oncogenes that mutate into oncogenes

Question 31

oncogene

Answer 31

when a normal gene mutates into a gain of function gene

Question 32

protein products of oncogenes and proto-oncogenes

Answer 32

oncogenes make oncoproteins proto oncogenes make proto oncoproteins

Question 33

Ras

Answer 33

a mutation in Ras turns it into an oncogene

Question 34

monomers

Answer 34

monomers have both tyrosine kinase and tyrosines to be phosphorylated. phosphorylated kinases can act as docking sites for other proteins

Question 35

SRC

Answer 35

non-receptor tyrosine kinase SH2 and SH3 are the 2 of the 4 domains that are involved in binding to other proteins

Question 36

what does sh2 and sh3 bind to

Answer 36

sh2: binds to short phosphotyrosine containing sequences in growth factor receptors and other phosphoproteins sh3: binds to target proteins through sequences containing proline and hydrophobic amino acids

Question 37

RAS pathways

Answer 37

1. activated RTK is binded to an adapter protein (GrB2) which is binded to Sos 2. Sos swaps GDP on the inactive Ras protein to GTP, activating it 2. RAS activates RAF (MAP kinase kinase kinase) 3. RAF activates MEK (MAP kinase kinase) 4. MEK activates ERK (map kinase) 5. when ERK is activated, it translocates to nucleus and activates different genes and transcription factors 6. this leads to changes in protein activity and changes in gene expression