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Biochem Block II Exam (Tulane SOM 2015) 2/3
Bichemistry Block II Set 2/3
71
Medical
Professional
10/03/2011

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Term
signal hypothesis
Definition
1. signal recognition particle (SRP) binds signal sequence on polypeptide
2. translation stalls/ SRP binds SRP receptor assoc. w/ translocon
3. GTP hydrolysis frees SRP and opens translocon
4. translation resumes, protein signal sequence cleaved inside membrane by signal peptidase
5. protein folds
Term
unidirectional protein translation across membrane due to these proteins
Definition
Sec63 complex
Hsp70 BiP
Sec63 + ATP + BiP = ratcheting of protein thru membrane
BiP also maintains open PP chain until translation complete to facilitate proper folding
Term
Type I membrane protein
Definition
single pass transmembrane protein inserted so that amino terminus faces lumen; signal sequence cleaved (Type III is the same except signal sequence not cleaved); peptide contain STOP TRANSFER ANCHOR SEQUENCE w/ hydrophobic residues that passes laterally through translocon to embed in membrane
Term
Type II membrane protein
Definition
single pass transmembrane protein inserted so that amino terminus faces cytosol; signal sequence not cleaved; like Type III, contains SIGNAL ANCHOR SEQUENCE flanked by positively charged residues that locate on cytosolic face
Term
Type IV membrane protein
Definition
multi-pass transmembrane protein; odd number of passes = ends on opposite sides
Term
GPI-linked protein
Definition
transmembrane proteins on extracellular side of membrane; protein inserted like Type I -> cleaved by GPI transamidase-> C' end attached to GPI anchor
Term
protein processing that occurs only in ER
Definition
disulfide bond formation
proper folding/ multisubunit assembly
Term
protein processing that occurs in the ER and Golgi
Definition
glycosylation
proteolytic cleavage
Term
O-linked glycosylation
Definition
first carbohydrate attaches to Ser or Thr w/ glycosyl transferases; ex: ABO blood groups
Term
N-linked glycosylation
Definition
attachment of preformed (on dolichol phosphate) carbohydrate structure to Asn of Asn-X-Ser/Thr by oligosaccharyl transferase (N = Asn)
Term
formation of oligosaccharide precursor
Definition
high mannose structure formed on dolichol phosphate starting in cytosol/ flips to ER lumen 1/2 way thru; 1st addition of MS by nucleotide sugar donor hydrolyzes UDP->UMP adding phosphate to base (2 total)
Term
tunicamycin
Definition
antibiotic that blocks addition of first MS by UDP-sugar donor, preventing formation of high mannose glycosylation structure (UDP-N-acetylglucosamine analog)
Term
signal that glycosylated protein is ready for ER -> Golgi transport?
Definition
glycosylases remove 3 glucose and 1 specific mannose in ER lumen
Term
what is the function of glycosylating proteins?
Definition
stabilizes protein (secreted proteins)
helps proper folding
cell-cell adhesion (ie CAMs)
Term
disulfide bond formation
Definition
2 cysteines bind via protein disulfide isomerase (PDI) in ER under oxidative conditions
Term
Calnexin, Calreticulin
Definition
sugar-binding lectins that maintain unfolding state until proper folding can occur
Term
Ero1
Definition
recycles PDI in disulfide bond formation process by oxidizing the molecule
Term
hyaluronic acid
Definition
aka hyaluronan; D-glucuronic acid + N-acteylglucosamine in beta1-3 and beta 1-4 linkages; not a proteoglycan
Term
chondroitin sulfate
Definition
D-glucuronic acid + N-acteyl-D-galactosamine w/ beta1-3 and beta1-4 linkages
Term
dermatan sulfate
Definition
L-iduronic acid + N-acetyl-D-galactosamine w/ alpha 1-3 and beta1-4 linkages
Term
keratan sulfate
Definition
galactose-6-sulfate + N-acetyl-D-glucosamine-6-sulfate w/ beta1-4 and beta1-3 linkages
Term
heparin/heparan sulfate
Definition
glucuronic acid or idouronic acid + N-acetylated or N-sulfated glucosamine w/ repeating alpha1-4 linkages
Term
Hunter Syndrome
Definition
MPS II; deficiency of iduronate sulfatase affecting "step 1" of DS and HS catabolism; treatment w/ Elaprase or Idusulfase
Term
Hurler Syndrome
Definition
MPS I; deficiency in alpha-L-iduronase affecting "step 2" of DS and HS catabolism; treatment w/ Aldurazyme or Laronidase
Term
San Filippo Type A
Definition
MPS III; deficiency in heparan-N-sulfatase affecting "step 3" of HS catabolism
Term
San Filippo Type C
Definition
MPS III; deficiency in acetyl-coa-acetyl-transferase affecting "step 4" of HS catabolism
Term
San Filippo Type B
Definition
MPS III; deficiency in alpha-N-acetyl-glucosaminidase affecting "step 5" of HS catabolism
Term
Morquio Syndrome A
Definition
MPS IV; deficiency in galactose-6-sulfatase affecting "step 1" of KS catabolism
Term
Morquio Syndrome B
Definition
MPS IV; deficiency in beta-galactosidase affecting "step 2" of KS catabolism
Term
peptidoglycan
Definition
disaccharide repeat of N-acteylglucosamine + N-acteylmuramic acid in beta1-4 repeats
Term
lysosomal acid hydrolases
Definition
function at pH range of 5-6
includes proteases, lipases, phosphatases, nucleases, glycosidases,
Term
pinocytosis
Definition
invagination, brings fluids into cell
Term
receptor-mediated endocytosis
Definition
invagination, ligand binds to receptors in clathrin-coated pit on cell membrane and is then brought into cell inside vesicle
Term
maturation of endosomes
Definition
after entry into cell with substrate, becomes acidified and enriched w/ lysosomal enzymes = lysosome
Term
phagocytosis
Definition
evagination that engulfs particle, internalizes w/i a membrane (macrophages, neutrophils)
Term
LDL particle structure
Definition
phospholipid membrane surrounding cholesterol w/ apolipoprotein B (ligand for LDL receptor)
Term
LDL receptor structure
Definition
NPXY sorting signal
beta-propellor domain attached to binding arm (at low pH is + and binds to arm)
Term
cellular uptake of iron
Definition
iron + apotransferrin = ferrotransferrin -> binds to transferrin receptor and brought into cell-> at lower pH Fe dissociates -> apotransferrin and transferrin receptor leaves cell -> neutral pH causes apotransferrin to dissociate from transferrin receptor to find new Fe
Term
multivesicular body
Definition
vesicle taken up by endosome through invagination, causing degradation of integral enzymes; ubiquinated Hrs proteins form ESCRT assembly to take in vesicles
Term
Hsc70
Definition
maintains unfolded protein for mitochondrial transport
Term
Tom proteins
Definition
transport outer membrane
Term
Tim proteins
Definition
Transport Inner Membrane
Term
targeting to mitochondrial matrix
Definition
matrix targeting sequence -> binds to Tom, translocated thru Tom40 -> translocated thru Tim proteins -> sequence removed by proteases
Term
targeting to inner mitochondrial membrane
Definition
Path A: hydrophobic stop sequence, moves laterally thru Tim pore (like Type I ER)
Path B: Oxa1 inner membrane protein + Oxa1 sequence in protein
Path C: multi-pass protein has multiple insertion sequences
Term
targeting to mitochondrial intermembrane space
Definition
Path A: proteins have matrix and inner membrane targeting (hydrophobic) sequences -> protease cleaves domain in intermembrane space
Path B: only intermembrane targeting sequence; no Tim interaction
Term
protein targeting to outer mitochondrial membrane
Definition
protein has stop transfer and outer membrane sequences, goes thru Tom40 and SAM
Term
peroxisomes
Definition
nuclear encoded
uses O2
peroxisome targeting: PTS1 Ser-Lyc-Leu or SKL at C'
Term
PTS1 targeting
Definition
pre-folded protein w/ PTS1 binds Pex5 in cytosol -> binds Pex receptor -> translocates thru Pex complex -> sequence not cleaved -> Pex 5 recycled
Term
3 important proteins involved in nuclear import
Definition
Ran (GTP-binding)
Importin-alpha (binds NLS)
Importin-beta (shuttles cargo)
Term
GEF
Definition
guanosine exchange factor that exchanges GDP for GTP
Term
GAP
Definition
GTPase activating protein- activates hydrolytic activity
Term
Ran-independent mRNA nuclear export
Definition
mRNP complex binds to Nxt1/TAP and nucleoporins -> mRNP remodeling + helicase activity of Dbp5 removes export complex -> Nxt1/TAP recycled via Ran-Importin mxn
Term
microfilaments
Definition
actin binds ATP
networks
polarized
tracks for myosin
contraction/ cortex network
Term
microtubules
Definition
alpha-beta tubulin binds GTP
rigid
polarized
tracks for kinesin, dynein
organization, long-range transport of organelles
Term
intermediate filaments
Definition
no nulceotide
tensile strength
unpolarized
no motors
cell, tissue integrity
Term
microtubule functions
Definition
mitotic spindle
interphase cellular structure
cellular transport
mvmt-cilia, flagella
Term
microtubule ring
Definition
13 protofilaments made of alpha- and beta-tubulin dimers
Term
MT stabilizing factors
Definition
Tau
MAP2 (+ charged, assoc. w/ microtubules; phosphorylation destabilizes microtubules)
Term
MT destabilizing factors
Definition
kinesin-13 family- binds + end dimers, monopolizes pool, promoting catastrophe
Op18/Stathmin- bends + end
Katanin- breaks microtubules exposing GDP caps
Term
nucleation of microtubules
Definition
gamma-tubulin
pericentrin
forms gamma-TURC
Term
centriole nucleating centers
Definition
pericentrin
gamma-tubulin
-form gamma-tubulin ring structure (gTuRC)
Term
kinesins
Definition
motor protein that moves - to +
ATP hydrolysis
Term
dyneins
Definition
motor proteins that move from + to -
ATP hydrolysis
Term
structure of dynein
Definition
stem-interacts w/ Dynactin (which binds cargo)
head-ATPase
stalk-microtubule binding site
Term
mvmt of flagella, cilia
Definition
outer and inner arm dyneins form axonemal complex; move on doublet microtubules connected by Nexin protein
Term
astral microtubules
Definition
function during mitosis to extend from/help orient spindle pole with respect to cell cortex/axis of cell division
Term
polar microtubules
Definition
attach to tips of chr.; function during mitosis to:
push duplicated chr. apart during prometaphase, help maintain spindle orientation, and push spindle poles apart during anaphase B
Term
kinetochore microtubules
Definition
function during mitosis to pull sister chromatids apart during anaphase A
Term
- end directed kinesin
Definition
only one example given- KinC; occurs during spindle pole migration in order to align polar MTs
Term
spindle pole migration
Definition
- end kinesin aligns polar MTs
+ end kinesin (BimC) pushes apart polar MT
- end dynein pulls astral MTs towards cortex
Term
CENP-E
Definition
kinesin in kinetochore that helps facilitate end capture of + end of kinetochore MT during mitosis
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