Midterm 3 (Chapters 9-15) Flashcards
what is plectin
a bridge made of an elongated dimeric protein that connects cytoskeletal filaments
what are the 3 major components of the nuclear envelope
nuclear pores, nuclear membranes, nuclear lamina
how does the nuclear envelope dissolute at the end of prophase
phosphorylation of human lamin causes de-polymerization and subsequent disassembly of the lamina
describe the structure of actin
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
cofilin
binds ADP actin and severs filaments
promoting depolymerization
profilin
- 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
thymosin
- sequesters G- actin preventing
polymerization - Displacement of thymosin allows binding
of G-actin to the plus end
thymosin
- sequesters G- actin preventing
polymerization - Displacement of thymosin allows binding
of G-actin to the plus end
F actin cycle
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
capping plus end vs capping minus end:
plus: prevents the filament from growing
minus: prevents the loss of subunits
arp2/3 complex
(actin related proteins) nucleate new branches off the sides of existing filaments. minus end attaches to filament
sarcomere
myosin overlaps, basic unit of muscle contraction, composed of actin and myosin
capZ
maintains attachment and caps
actin at plus end
Troponin complex
binds to tropomyosin Both have regulatory roles in contraction
Tropomodulin
caps the (-) end
Myomesin
bundles the myosin
filaments
Nebulin
consists of repeating actin
binding motifs, dictates the length of an
actin (thin) filament and binds filament
to Z line
Titin
extends through the myosin
(thick) filament and attaches to the Z
disk – helps to prevent tearing of
muscle
extracellular signal to cellular response pathway
- synthesis of the signalling molecule
- release of the signalling molecule via exocytosis
- transit of signalling molecule to the target cell
- binding of signalling molecule (ligand) to a protein receptor on the target cell
- binding of ligand to receptor results in a conformational change of the receptor
- receptor initiates one or more intracellular pathways
- deactivation of the receptor
- removal of the ligand
describe 4 types of intracellular signalling
- endocrine: messenger molecules reach their target cells through the bloodstream (insulin)
- paracrine: messenger molecules travel short distances through extracellular space (neurotransmitters)
- autocrine: cell has receptors on its surface that respond to the messenger (t-cells during immune response)
- juxtacrine: short range but requires physical contact between sending and receiving cells (antigen presentation)
2 types of receptors
- cell surface receptors
- intracellular receptors
what is a second messenger
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
phosporylation
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
GTPase superfamily
enzymes that hydrolyze GTP to GDP
molecular switches
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
G protein coupled receptor (GRK)
GRK phosphorylation sites for receptor downregulation. sites of phosphorylation in the cytosol so OOC- can bind
what does active G protein do
binds to an effector protein
G proteins activate adenylyl cyclase
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
since kinase A phosphorylates so many things,
it is often sequestered in certain parts of the cell to keep the signal targeted (AKAPs - A Kinase anchored protein)
signal transduction by RTKs is usually terminated by:
internalization of the receptor primarily through clathrin-mediated endocytosis
gain of function mutation
proto-oncogenes that mutate into oncogenes
oncogene
when a normal gene mutates into a gain of function gene
protein products of oncogenes and proto-oncogenes
oncogenes make oncoproteins
proto oncogenes make proto oncoproteins
Ras
a mutation in Ras turns it into an oncogene
monomers
monomers have both tyrosine kinase and tyrosines to be phosphorylated. phosphorylated kinases can act as docking sites for other proteins
SRC
non-receptor tyrosine kinase
SH2 and SH3 are the 2 of the 4 domains that are involved in binding to other proteins
what does sh2 and sh3 bind to
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
RAS pathways
- activated RTK is binded to an adapter protein (GrB2) which is binded to Sos
- Sos swaps GDP on the inactive Ras protein to GTP, activating it
- RAS activates RAF (MAP kinase kinase kinase)
- RAF activates MEK (MAP kinase kinase)
- MEK activates ERK (map kinase)
- when ERK is activated, it translocates to nucleus and activates different genes and transcription factors
- this leads to changes in protein activity and changes in gene expression
