Protein Folding/Modification/Processing/Degradation

glycoproteins

proteins with sugars as post=translational modifications

N-linked glycoprotein

reducing end of a GlucNAc gets attached to asparagine N

O-linked glycoprotein

often GalNAc, attached to Ser/Thr O

• important for secreted/cell surface proteins

why does glycosylation occur?

• solubility

• immunological (self/non-self) detection

• recognition/receptor binding events

• folding/stability

are O-linked sugars normally alpha or beta?

alpha

all N-glycosidic protein attachments occur through what type of bond?

beta-N-acetylglucosamino-Asn

sialic acid

N-acetylneuroaminic acid

what type of sugar is fucose?

L

proteins that are meant to remain cytosolic are translated by:

free ribosomes

proteins destined for the cell surface are directed by:

signal sequence in protein

signal sequence in protein directs ribosome for proteins destined for the cell surface to:

ER

SRP

signal recognition peptide

first step of synthesis of core oligosaccharide of glycoproteins

build oligosaccharide by successive addition of monosaccharide units

translocation in synthesis of core oligosaccharide of glycoproteins

moves incomplete oligosaccharide across membrane

where do first steps of synthesis of core oligosaccharide of glycoproteins occur?

cytosol outside of ER

where is synthesis of core oligosaccharide of glycoproteins completed?

lumen of ER

describe synthesis of nuclear proteins

• entire protein is translated

• N-terminal nuclear localization signal causes transport to the nucleus

glycophorin A

• transmembrane protein on the cell surface of erythrocytes

• coats cell surface with sialic acid sugars

  → in diabetes, chronically high glucose levels spontaneously glycosylate

importance of folding

protein has to assume correct secondary and tertiary structure

native (functional) structure of a protein must be a _________ form

stable

is a polypeptide backbone hydrophilic or hydrophobic?

hydrophilic

why is there an energetic cost to folding a protein?

most of it becomes inaccessible to water

is folding entropically favorable or unfavorable?

unfavorable

how are polar amides stabilized in a folded protein?

hydrogen bonding to other amides in secondary structure

how are polar side chains stabilized when interior?

dipole or hydrogen bond interactions with other polar groups

why do cellular proteins exist?

to help fold, re-fold, or destroy misfolded proteins

• include heat shock proteins

amyloidosis

accumulation of misfolded/denatured protein