membrane protein topology

Question 1

when are characteristic topologies of membrane proteins established?

Answer 1

during biosynthesis

Question 2

what is on membrane proteins outside of the cell?

Answer 2

disulfide bonds, sugars/carbs, glycolipids (note they are all charged)

Question 3

sec61 complex

Answer 3

protein translocator on ER membrane

Question 4

how to integrate a single pass transmembrane protein into the ER membrane

Answer 4

N-terminal start transfer sequence and internal stop transfer sequence.

Question 5

internal stop transfer sequence

Answer 5

hydrophobic so it gets stuck in the membrane. anything on other side stays in cytosol.

Question 6

one internal start transfer sequence

Answer 6

a way to integrate a single pass transmembrane protein into the ER membrane. the positive end of the transfer sequence always stays in the cytosol. The negative heads to the ER lumen, which means that it will be on the outside of the cell.

Question 7

inserting a multipass membrane protein/ rhodopsin

Answer 7

has start sequence and and then start and stop sequences. all function of info encoded in rna translated in the protein, which signals how protein will go into ER membrane.

Question 8

GPI anchor proteins

Answer 8

added to some proteins in the ER. protein. makes it easier to cut out. attached by a phospholipid.

Question 9

modified protein

Answer 9

all the modifications happen in the ER and golgi

Question 10

modifications in the ER lumen

Answer 10

cleavage of signal peptides
co-translational N-glycosylation
Trimming of N-linked sugarsqauli
hydrosxylation (pro, lys of collagens)
disulfide bond formation
protein folding
assembly of multimeric proteins

Question 11

addition of N-linked oligosaccharides

Answer 11

process of translation is rapid. most sugars are added one at a time, prefab structure.

Question 12

Bip (Hsc70)

Answer 12

facilitates folding by binding transiently to new proteins in order to keep them unfolded and prevent misfolding or aggregation

Question 13

calnexin, and calreticulin

Answer 13

chaperone proteins; promote and monitor folding by cyclical binding to a terminal glucose in N linked oligosaccharides

Question 14

cystic fibrosis

Answer 14

delta508F; amino acid change. one protein with complex folding pattern. creates a protein that cannot properly fold. even though cl channel aspect, it never gets to where it needs to function. stuck in ER and targeted for degradation

Question 15

cellular quality control

Answer 15

retrotranslocation to cytosol and degradedby proteasoms (ERAD), receives polyubiquitin chain and heads to proteasone;
upregulation of chaperones
also ER stress management/quality control (sends to apoptotic death)
unfolded protein response (UPR)
ER overload response (EOR)

Question 16

PDI or protein disulfide isomerase

Answer 16

catalyzes the formation of disulfide bonds so that the most stable conformation is achieved.

Question 17

ER resident proteins

Answer 17

present in ER in high conc. /retained by mechanism that retrieves them if they escape into the cis golgi/ have c terminal Lys-Asp-Glu-Leu sequence recognized by KDEL receptors in the membranes of small transport vesicles shuttling bet. ER and early golgi. and then used to return proteins to ER.

Question 18

what causes cystic fibrosis

Answer 18

mutations in CFTR, cystic fibrosis transmembrane conductance regulator. most common mutation is a phenylalanine deletion, delta508, which is found in 70% of cf individuals

Question 19

unfolded protein response (UPR)

Answer 19

production of chaperones is upregulated through the activation of a unique signaling ER sensor and signal transduction mechanism.