Biochem - Protein Synthesis

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what are the 5 stages of translation?: activation of AAs in cyto
initiation (ribosome)
elongation (ribosome)
termination (ribosome
co/post translational processing
what is the Adaptor Hypothesis?: anti-codon of tRNA base pairs with the codon of mRNA in an ANTI-PARALLEL fasion
in which direction is the mRNA read by the tRNA?: 5' to 3'

read sequentially..commaless
on which end of the tRNA is the AA attached?: 3'
in which direction does protein synthesis occur?: N terminus to C terminus
what is the difference between the start signals and their corresponding AA's in euk and prok?: AUG is start codon for both

euk use Met
prok use formylated Met (fMet)
what are the stop/nonsense codons?: UAA
UAG
UGA
which two AA's are designated by a single codon?: methionine (AUG)
tryptophan (UGG)
what is degeneracy?: multiple codons for single AA

first two bases predominate in tRNA selection, 3rd base (3' end) is not as significant
what is the advantage of degeneracy of the genetic code?: protect against point mutations (in the 3rd base)
what does it mean when the genetic code is unambiguous?: a given codon can code for only ONE amino acid
what is the wobble hypothesis?: pairing b/w codon and anti-codon adheres to the usual Watson-Crick base-pairing rules at the FIRST TWO bases, but is less stringent for the third
what can a single tRNA recognize?: can recognize more than one codon, but NOT necessarily every codon corresponding to a given AA
what happens when the first base of the anti-codon of the tRNA is modified by deamination?: still can base pair with the codon because of the wobble hypothesis
what does it mean when the genetic code is "quasi-universal"?: mitochondria use different genetic code (UGA -> Trp)
however it is UNAMBIGUOUS

mitochondria in different species also use different genetic code
what is a silent mutation?: point mutation in the 3rd position of a degenerate codon, with no change in AA
what is a missense mutation?: point mutation w/ incorporation of a different AA
what kind of mutation does sickle cell disease have?: missense mutation in the hemoglobin beta chain

homozygous
what is a nonsense/terminator mutation?: point mutation producing a STOP codon
what mutation is involved in hemoglobin McKees Rocks?: nonsense mutation, resulting in a protein that is 2 AA's shorter

causes truncated protein w/ unusually high oxygen affinity, increasing RBC production

polycythemic phenotype
what mutation is involved in beta thalessemias?: terminator mutations
what are the characteristics of the acceptor stem in tRNA?: at the 5'/3' area of the clover leaf (top)

7 bp stem w/ some non-Watson-Crick bp's

on the 3' end, it ends w/ CCA and is attached to a specific AA
what are the characteristics of the D loop in tRNA?: 3-4 bp stem w/ dihydrouridine

on left side
what are the characteristics of the anticodon loop in tRNA?: 5 bp stem that ends in a loop that contains the anticodon
what are the characteristics of the variable loop?: may differ in length (65-110 nt)
what are the characteristics of the TÏˆC loop?: 5 bp arm w/ loop that contains TÏˆC (Ïˆ is psuedouridine)

on the right
what do the modified nucleotides do?: affect tRNA structure and stability

contribute to efficiency of codon recognition
what are the steps for charging the tRNA?: 1. formation of enzyme bound aminoacyl-AMP: aminoacyl tRNA syntetase brings ATP and its cognate AA to form enzyme-bound AA~AMP and pyrophosphate

2. formation of aminoacyl~tRNA: enzyme-bound AA~AMP reacts w/ cognate tRNA by forming ESTR$ linkage b/w carbonyl grp of AA to the 2' or 3' OH of adeosine at the 3' end of tRNA.

results in a high energy bond b/w AA and tRNA

AA loses identity
what does the aminoacyl tRNA synthetases do?: there are 20 different types, each recognizing ONE AA and ALL of its cognate tRNAs

they charge the tRNA
what is the charging of the tRNA driven by?: driven by hydrolysis of PPi (pyrophosphate)i to 2Pi
what kind of bond is formed b/w the AA and tRNA: high energy ester linkage b/w carbonyl grp of AA and OH grp of adenosine at 3' terminus of tRNA
how many ATP are used up to charge a single tRNA?: 2 ATP used in activation step
when does an AA lose its identity?: once it is charged on the tRNA

it cannot undergo any metabolic changes except going to the ribosome for protein synthesis
what does the aminoacyl-tRNA synthetase have to recognize?: it must recognize specific tRNAs as well as specific amino acids.

specifically recognizes the correct anticodon on the tRNA
what are the catalytic sites on the aminoacyl-tRNA synthetase?: 1. synthetic site

2. hydrolytic site - destroys incorrectly formed AA~AMP or AA~tRNA (editing) -> high fidelity!
what are the components of the prokaryotic ribosome?: 70S w/ 30S and 50S subunits

30S subunit = 16S rRNA + 21 proteins

50S subunit = 23S rRNA + 5S rRNA + 34 proteins
what are the components of the eukaryotic ribosome?: 80S w/ 40S and 60S subunits

40S subunit = 18S rRNA + 34 proteins

60S subunit = 5.8S rRNA + 28S rRNA + 50 proteins + 5S rRNA(from pol III)
what proteins do free ribosomes synthesize?: proteins that remain in the cytosol or become targeted to the nucleus, mitochondria or peroxisomes
what proteins do membrane bound ribosomes synthesize?: proteins that will be secreted from the cell or detined for the endomembrane system (ER/Gogli/cell mbn)
what is a polyribosome (polysome)?: many ribosomes associated w/ a single mRNA
describe the three binding sites on the tRNA: A (aminoacyl) site - accepts incoming aminoacylated tRNA

P (peptidyl) site - holds tRNA to which the growing peptide is attached

E (exit) site - temporarily holds the deacylated tRNA until it exits
what is the small subunit of the ribosome responsible for?: formation of the initiation complex

decoding the genetic info

controlling the fidelity of codon-anticodon pairing
what is th large subunit of the ribosome responsible for?: contains the peptidyl transferase site that catalyzes petpide bond formation

has a tunnel through which the nascent peptide is threaded
what is the process of initiation of translation in euk?: 1. eIF-2 binds to GTP and met~tRNA(met) to form a ternary complex

2. 40S subunit (bound to eIF-3) joins complex, aided by eIF1 and eIF1a

3. PRE-INITIATION COMPLEX:
mRNA (+ eIF-4 family, poly-A-binding protein, and eIF5) joins complex.
mRNA scanned to look for 1st AUG after 5'cap (requires eIF4 proteins and ATP hydrolysis)

4. INITIATION COMPLEX:
60S subunit joins as eIF-3, eIF-1, eIF-1a, and eIF-5 leave.
eIF-5b-GTP comes in and leaves w/ hydrolysis.
eIF-2-GTP is hydrolyzed to eIF-2-GDP and is released.
what does eIF-3 do?: it is an anti-association factor

aids dissociation of subunits at the ned of translation

blocks association of 40S and 60S subunits
how is active eIF-2 regenerated?: regenerated by a GDP-GTP exchange that is facilitated by eIF-2b (guaning nucleotide exchange factor)

eIF-2-GDP + (eIF-2b + GTP) -> eIF-2-GTP + (eIF-2b + GDP)
what do eIF-4s do?: recognize and bind the 5'cap of mRNA

help place mRNA on the 40S subunit w/ the 5' cap correctly oriented
where in the ribosome does the tRNA(i) first go?: only tRNA that first goes to the P site
what is the end result of initiation?: 80S ribosome complex w/ mRNA

met~tRNA(i) at P site
what are the differences in translation initation in prok and euk?: prok: fewer non-ribosomal factors

rely on base pairing b/w purine rich Shine-Delgarno seq in mRNA and pyrimidine-rich seq in 16S rRNA.

no ATP hydrolysis b/c no scanning of mRNA to locate AUG.

only 1 GTP used in initiation.
what are the steps in euk elongation of translation?: 1. aa~tRNA of next codon is brought to A site by EF-1α-GTP (GTP hydrolyzed to GDP).

2. ribosomal peptidyl transferase (ribozyme of large subunit) transfers initiating met from its carrier tRNA to α-amino grp of AA of AA~tRNA at A site. Forms peptide bond.

3. peptidyl tRNA occupies hybrid A/P site and deacylated acceptor stem of tRNA(i) is displaced to E site.
EF-2 (translocase) moves messenger and dipeptidyl tRNA from A site to P site (GTP hydrolysis)

4. mRNA-peptidyl tRNA complex fully translocated to P site. Deacylated initiator tRNA moved to E site
how is active EF-1α regenerated?: active EF-1α (which has a GTP) is regenerated by guanine nucleotide exchange w/ EF-1βγ
how is elongation of translation between prok and euk different?: the same, except for different names for factors:

EF-1α = EF-Tμ
EF-1βγ = EF-Ts
EF-2 = EF-G
what is the function of EF-2?: translocase that moves peptide~tRNA from A to P site
what is the function of EF-1α?: brings next AA~tRNA to the A site
what is the process for termination of elongation in euk?: 1. when ribosome encounters STOP codon, eRF1 binds stop codon at or near A site

2. peptidyltransferase now fxns as hydrolase; new protein is released by hydrolysis of ester bond

3. eRF3-GTP joins ribosomal complex, GTP is hydrolyzed, and eRF1 is released from complex.
other factors join and facilitate release of mRNA.
how is termination of translation between prok and euk different?: prok have 3 releasing factors (RFs) involved

2 of them are used to recognize STOP codons (euk only have 1)
how much energy is used in the charging of tRNA, and where is it done?: 2 ATP (euk + prok)

cytosol
how much energy is used in initiation of translation, and where is it done?: prok: 1 GTP
euk: 2 GTP + ATP

ribosome
how much energy is used in elongation of translation, and where is it done?: 2 GTP/bond (euk + prok)

ribosome
how much energy is used in termination of translation, and where is it done?: 1 GTP (prok + euk)

ribosome
when does formylation of methionine occur in prok?: formylation occurs AFTER the methionine is attached to the initiating tRNA.

formyl grp is carried by tetrahydrofolate and rxn is catalyzed by transformylase
describe transcription and translation coupling in prok.: 5' end of mRNA can base pair w/ 16S rRNA of 30S subunit while mRNA is still being transcribed
if prok transcription is inhibited by an inhibitor, what happens to translation? what happens to transcription if translation is inhibited?: translation is also inhibited

if translation is inhibited, the transcription process MAY be affected
why are transcription and translation not coupled in euk?: transcription and processing of hnRNA is in nucleuse.
translation is in cytoplasm.

only complete mRNAs may be translated
how do eukaryotes ensure that an mRNA is complete before translation begins?: euk mRNA may circularize

eIF-4E recognizes the 5' end of mRNA.
PAB interacts w/ poly A tail at 3' end.
eIF-4G (scaffold protein) link eIF-4E and PAB.

eIF-4F is involved also.
what are the methods for controlling initiation of translation in euk?: phosphorylation of eIF-2

regulation of eIF-4e

mRNA masking
what does phosphorylation of eIF-2 do?: when eIF-2 is phosphorylation (under AA starvation, heme deficiency, ER stress, or dsRNA), leads to shutdown of translation and cell cycle arrest and/or apotosis

phosphorylated eIF-2 sequesters eIF-2b, leading to inactivation of available eIF-2b and termination of translation initiation
what does regulation of eIF-4e do?: proteins such as 4E-BP (eIF-4e binding protein) which block the interaction of eIF-4e w/ other members of the eIF-4f complex can inhibit this activity

blocks initiation of translation

4E-BP activity is regulated by phosphorylation. when 4E-BP is phosphorylated, it is inactive and translation is stimulated
what does mRNA masking do?: regulates translation of a SPECIFIC mRNA

proteins interact w/ eIF-4e and components of the 3'end of mRNA -> mRNA is put into a stable but untranslated state.

factors release w/ signal.
what are the methods for controlling elongation of translation in eukaryotes?: diphteria toxin
Pseudomonas-toxin

both inactivate EF-2.

protein toxins bind to cell mbn, then enter cell. Toxin catalyzes ADP RIBOSYLATION of EF-2, inhibiting the trnaslocation activity.
what does puromycin do?: causes premature termination in BOTH euk and prok

resembles AA~tRNA and binds at A site
what does cyclohexamide do?: inhibits EUKARYOTIC peptidyl transferase activity.

interacts only w/ 60S subunit, preventing peptide bond formation.
what does streptomycin and related aminoglycosides do?: at high conc: inhibits translation INITIATION.
binds to 30S subunit and interfere w/ binding of fmet-tRNA to P site

low conc: MISREADING of mRNA

streptomycin sensitivity is on protein S12 on the 30S subunit.
what do tetracyclines do?: bind to 30S subunit

interfere w/ binding of incoming AA~tRNA to A site

elongation inhibited
when does formylation of the methionine occur in prok translation?: formylation occurs after the methionine is attached to the initiating tRNA

formyl grp is carried by tetrahydrofolate and the rxn is catalyzed by transformylase
in prok, what happens when transcription is inhibited?: translation is inhibited as well.

however, if translation were inhibited, transcription may or may not be affected
why are transcription and translation in euk not coupled?: transcription and processing of hnRNA is in nucleus, translation is in the cytoplasm
how does a eukaryote ensure that an mRNA is complete before it initiates translation?: mRNA most likely circulizes

eIF-4E recognizes the 5' end of mRNA, and PAB interacts w/ 3' poly A tail.
eIF-4G (scaffold protein) links eIF-4E and PAB, ensuring complete mRNA

this is all in a complex w/ eIF-4F
what are the methods for controlling initiation in euk?: phosphorylation of eIF-2

regulation of eIF-4e

mRNA masking
how is eIF-4e regulated?: proteins such as 4E-BP (eIF-4e binding protein) blocks the interaction of eIF-4e w/ other members of the eIF-4f complex

blocks initiation of translation

4E-BP activity is regulated itself by phosphorylation; phosphorylated 4E-BP is inactive, stimulating translation
what is mRNA masking?:: regulates translation of a SPECIFIC mRNA

proteins interact w/ eIF-4e and components of 3'end of mRNA, puting mRNA in a stable but untranslated state.

once signal is given, factors release.
what are the mechanisms for controlling elongation in euk?: diphteria toxin
pseudomonas-toxin
how do diphteria toxin and pseudomonas toxin inhibit protein synthesis in euk?: bind to cell mbn, then enter cell.

toxin catalyzes ADP RIBOSYLATION of EF-2, inhibiting translocation activity
what does cycloheximide do?: inhibits euk peptidyl transferase

interacts w/ 60S subunit, preventing peptide bond formation
what are the antibiotics that inhibit translation in euk?: puromycin (both euk and prok)

cyclohexamide
what does streptomycin and related amingolycosides do?: high conc: inhibits translation inhitiation.
bind to 30S subunit and interfere w/ binding of fmet-tRNA to P site

low conc: misreading of mRNA by interacting w/ 30S subunit

sensitivity lies in protein S12 of 30S subunit
what do streptomycin resistant strains of bacteria have?: protein S12 of 30S subunit is altered, preventing binding of streptomycin
what do teteracyclines do?: bind to 30S subunit and interfere w/ binding of incoming AA~tRNA to the A site

elongation phase is inhibited
what does chloramphenicol do"?: inhibits peptidyl transferase rxn in prok and MITOCHONDRIAL protein synthesis.

inhibits catalytic activity by interacting w/ 23S rRNA of 50S subunit

toxic! only for severe cases of infection
what does erythromycin do?: narrows the entrance of tunnel in 50S subunit

sensitivity resides in 23S rRNA
what do erythromycin resistant strains of bacteria have?: methylated base (A) in the 23S rRNA, so that erythromycin cannot bind 50S subunit
what does buyS AT 30, CELLS at 50 mean?: buy
S = Streptomycin

A = Aminoglycosides
T = Tetracyclines

30S subunit

------
C = Chloramphenicol
E = Erythromycin
L = cLindamycin
L = Linezolid
S = Streptogramins

at 50S subunit
what is the general mechanism for targeting cellular organelles?: 1. cytosolic recognition of the signal

2. interaction w/ receptor at the target site

3. NTP-dependent translocation across the targt mbn
which proteins are targeted co-translationally?: proteins destined for secretion, the plasma mbn, ER, golgi, and lysosomes
which proteins are targeted post-translationally?: proteins destined for nucleus, mitochondrion, or peroxisomes
where is the signal sequence of leader sequence on proteins that are to be secreted?: on the N-terminal portion of the protein

10-40 AA; hydrophobic
what are the steps for Signal Peptide Recognition?: 1. hydrophobic signal seq emergences from a cytosolic ribosome

2. signal seq interacts w/ signal recognition particle (SRP: 7S RNA molecule w/ 6 proteins); causes elongation arrest

3. complex attaches to SRP receptor (docking protein) on cytosolic face of RER

4. ribosome+nascent polypeptide is delivered to the translocation machinery or translocon (Sec61) for passage through the RER mbn (GTP hydrolysis); as the SRP is released and recycled, translation resumes
what are the steps for co-translational targeting of secreted proteins?: 1. Signal Peptide Recognition

2. signal seq is removed by signal peptidase

3. protein is sequestered in vesicles that bud off from the RER and move to and through the Golgi

4. in absence of any more signals, protein is secreted from the cell
what are the steps for co-translational targeting of ER-resident proteins?: retention processes not well defined

retrieval pathway:
C-terminal KDEL serves as retrieval signal, allowing proteins to be retrieved from the Golgi and returned to ER
what are the steps for co-translational targeting of integral/transmbn proteins?: threading of protein through RER mbn stops due to "stop transfer" or "mbn retenion" sequences in protein

stop transfer seq is a hydrophobic stretch of 22 AA, spanning mbn as alpha helix

if destined for non-ER mbns, vesicles bud off

default: plasma mbn
what are the steps for co-translational targeting of lysosomal proteins?: 1. glycosylated in the ER lumen

2. in Golgi, a terminal mannose residue on the oligosacc is phosphorylated C#6 involving UDP-GlcNac.

3. Mannose-6-PO4 binds to receptors in the GOlgi, recptors cluster, bud off, and fuse w/ sorting vesicles

4. low pH cause dissociation of glycoprotein from mannose-6-PO4 receptor, and phosphatase removes phosphate

5. vesicles w/ lysosomal enz fuse w/ lysosomes
what is I-cell disease?: rare autosomal recessive lysosomal storage disease

lack of mannose 6-P targeting signal, caused by lack of phosphotranserase

lysosomal acid hydrolases are then secreted by default into blood.

lysosomal inclusions form b/c no enz

skeletal abnormalities, pyschomotor retardation
what is the mechanism for post-translational targeting to the nucleus?: 1. Nuclear Localization Sequence (NLS) of basic AA residues (usu interal seq) is recognized and bound by cytosolic proteins (alpha and beta importin)

2. tripartite coplex docks to and is translocated through nuclear pore complex. GTP-dependent and depends on Ran, which associates AFTER going through NPC.

3. Importins recycle to the cytosol.

4. NLS is NOT cleaved
what is a nuclear export signal (NES)?: signal on a protein that can facilitate removal from nucleus.

reversal of import pathway
what is Sweger Syndrome?: mutation in NLS of the SRY protein (on Y chrom)

SRY w/ mutated NLS cannot enter nucleus -> no testis development signals

XY indiv born as female
what is the mechanism for post-translational targeting to the mitochondria?: 1. protein enters mit via interaction of N-terminal Mitochondrial Entry Signal or Matrix-Targeting Signal

2. Entry signal (short and basic) forms an N terminal amphipathic alpha helix

3. protein-receptor complex moves laterally in outer mbn to site where outer and inner mbns in contact

4. heat shock proteins UNFOLD protein via TOM and TIM (w/ ATP)

5. signal seq cleaved by peptidase
what is Human Deafness Dystonia Syndrome?: defect in DDP (deafness dystonia protein), one of the proteins in the TIM complex.

X-linked recessive

progressive deafness, blindness, dystonia, and dysphagia
what are the necessary components for bringing a protein into the mit matrix?: heat shock proteins/chaperones

electrochemical H+ gradient

ATP
what is the mechanism for post-translational targeting to peroxisomes?: 1. PTS1 signal is a C-TERMINAL TRIPEPTIDE (SKL). PTS2 (N-terminal nonapeptide) is also known. Requires peroxines (encoded by PEX genes), which are chaperones and soluble PTS receptors

2. similar to targeting to nucleus, but no NPC
what is Zellweger's Syndrome?: an AR disorder caused by inability to target proteins to peroxisomes

neurological impairment
early death (1yr)
what are examples of covalent modifications to proteins?: ADP-ribosylation, Phosphorylation, Acetylation, carboxylation, hydroxylation (collagen), sulfation (collagen), methylation, iodination, ubiquitination, SUMOlation, glcosylation
what are the two types of glycosylation, the most common covalent modification of proteins?: O-glycosidic linkages to OH grps on ser or thr residues or on hyl in collagen

N-glycosidic linkages to amide NH2 grp on asn in seq asn-x-thr/ser
how are sugars attached to proteins through an O-glycosidic link?: uses nucleotide sugars (UDP or GDP-sugar)

occurs after protein has reached Golgi; stepwise donation of sugars by glycosyltransferases to create oligosacc of varying lenghts; GalNAc is initial sugar

occurs in cytosol, donation of a monosacc
how are sugars attached to proteins through an N-glycosidic link?: uses branched, preassembled oligosacc (14 sugar residues) linked to DOLICHOL PHOSPHATE, a lipid associated w/ ER mbn

begins in ER through en bloc transfer of oligosacc

trimming occurs in ER (glc) and Golgi (mannose), resulting in a COMMON pentasacc core (2GlcNAc + 3 mannose)

additional modific occur in Golgi
what does tunicamycin do?: inhibits attachment of sugars to proteins through an N-glycosidic link
what are the functions of glycosylation?: increase solubility
protect against proteolysis
influence spatial organization
involved in recognition and antigenicity
what are Congenital Disorders of Glycosylation (CDG)?: grp of disorders w/ defect in ability to synthesize N-linked proteins b/c defect in synethesis or transfer of oligosacc (ER) or in modification rxns (Golgi)
what is glycosylphosphatidyl inositol (GPI) anchor?: GPI anchors tether certain proteins to the outer face of the euk. plasma mbn
what is paroxysmal nocturnal hemoglobinuria?: deficiency in GPI-linked proteins in RBC

RBC cells destroyed -> urine
what are the classes of heat-shock proteins in euk?: hsp70 (includes BiP) and hsp60

both have high affinity for exposed hydrophobic patches

both use ATP hydrolysis
how are disulfide bond formed?: via protein disulfide isomerase (PDI), an enzyme of the ER
how are unfolded proteins recognized?: ER unfolded-protein-sensing factors (such as PERK, ATF-6, and IRE 1) recognize unfolded proteins in ER.

transcription of chaperone mRNAs is increased.

translation is inhibited

proteins (ie. UDP-glucose, glycoprotein glucosyl transferase) redirect unfolded protein to glycosylation pathways to try to refold
what happens when attempts to correct unfolded proteins are futile?: ER-associated degradation (ERAD) pathways

protein is ejected into cytosol.
residual glycosylation is removed.
protein is degraded.
what are some diseases that result from misfolded proteins?: CF
neurodegenerative disorders (Alzheimer, Parkinson, Huntington)
how does cleavage of peptide bonds work?: removal of initiating methionine

removal of signal seq: preprotein to proprotein

conversion of proproteins to functional (native) proteins

ex: insulin
what are cathepsins?: proteases that mediate lysosomal degradation (non-selective)
what are the steps for cytosolic degradation of proteins?: ATP-dependent

1. Proteins selected for degradation through ubiquitinylation

2. degraded in ATP-depended process in 26S PROTEASOME
how are proteins ubiquinylated?: 1. formation of AMP-ubiquitin, which combines with enzyme E1

2. E1 leaves, E2 is added

3. E2 brings ubiquitin to E3.protein, where E3 catalyzes addition of ubiquitin to the protein

4. more ubiquitins added; at least 4 necessary
how are proteins marked for ubiquitin-mediated degradation?: N-end rule: destabilizing AAs such as arg have short 1/2 lives

internal PEST sequences
describe the proteasome: 26S proteasome

20S catalytic core: portease w/ broad specificity

19S regulatory caps: recognize ubiquitin tag; unfold and thread protein into core and release ubiquitin, ATP hydrolysis
what is bortezomib?: porteasome inhibitor

treats multiple myeloma
what are the three domains of the nascent prepropeptide alpha chain of collagen?: Domain 1: met, singal seq, and an N-terminal globular propeptide

Domain 2: C-terminal globular propeptide

Domain 3: left-handed helix (Gly-X-Y)
where are the proline and lysine residues hydroxylated (collagen)?: inside lume on RER

dependent on seq, requires hydroxylases, oxygen, Fe+2, vit C (ascorbate), and alpha-ketoglutarate
what are some covalent modifications that collagen has gone through?: O-glycosidic linkages
N-glycosidic linkages
hydroxylation (of pro and lys)
what is procollagen?: triple helix (C to N termini) of hydroxylated L-handed alpha chains
what is the significance of hydroxyproline in collagen?: formation of triple helix will not happen w/o hydroxyproline

hydroxyproline is UNIQUE to collagen
what is tropocollagen?: procollagen w/ N- and C- terminal globular parts have been cleaved by proteases in the extracellular matrix
how are collagen fibrils formed?: tropocollagen molecules cross-link via lysyl oxidase, which deaminates lys and hyl residues to form reactive aldehydes
what is Osteogenesis Imperfecta?: brittle bone disease

mutations in two genes that code for type I alpha chains

Type II is lethal - massive loss of protein

Type I is milder
what is Ehlers-Danlos Syndrome?: elastic skin

Type VI: deficiency in lysyl hydroxylase

Type VII: mutations that eliminate cleavage of N-terminal propeptide cut sited
what is scurvy?: deficiency in vit. C

due to decrease in hyp and hy

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