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NBME 21 Answers

nbme21/Block 3/Question#28 (71.8 difficulty score)
A 1-year-old girl is admitted to the hospital ...
Disruption of the secondary structure of collagen molecules🔍
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 +14 
submitted by wasabilateral(41),
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I kithn ti hsa oenmghits ot do ihtw enyilcg eu(d ot tsi malls isez it anc tfi ni yamn scapel weher toreh oinam acdsi nac not nda enche it isopderv ur“scatltur ncsamtcpso”e ot teh c,leolgna .ei. ptu a kkin in teh alhpa e.)xihl If necgyli is apdicesml by ohinestmg se,el I dnot’ nkiht gelraocn-pol can rofm sti terocrc esracdoyn ctuturer.s

jotajota94  True! also, glycine is 1/3 of collagen alfa chains, so it makes sense that substitution with alanine (which is much bigger) would lead to disruption in the alpha helix formation. +  
jotajota94  True! also, glycine is 1/3 of collagen alfa chains, so it makes sense that substitution with alanine (which is much bigger) would lead to disruption in the alpha helix formation. +  
thepacksurvives  Glycine is small and bendy, which allows it to form the fibrils for the triple helix +  
brasel  Also in general (FA 2018 pg 50) OI is from problems forming the triple helix which is secondary structure. Fortunately, they gave us something to reason with in the question (Gly->Ala) +2  



 +11 
submitted by cellgamesgojan(40),
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I f,geriud -ieycX-gYnl si ahcnlltyice neroediscd a p“rmayir iaonm cadi cruteurts fo a o”pnteri scnei het itdniionef of a yrraPim curerutts fo a inperto is a“ ralnie hacin fo noami ”is.dac fI yuo sems ihtw hte rmPriya useurrttc, sa in the uiqtenso met,s uyo ctaonn ormf hte ondecSayr rusreuctt fo the t,epoirn hcwih si deeirtemnd by teh dg-onnheoyndgirb hhwci csuroc ewbntee the iteppde cboakebn, tepednnneid fo eht R r.sguop I opeh htis emda .nsees

moFr daiwipkie: caroSnyd“e rretutcus si lfyrlamo iedfedn by the ttrnpea of dgyohner sobdn nbeweet het omani endghyor dan loxycarb genyox tsoma ni teh epedpit kbncobea.” sam(ehsip m)nei


From Molecular Biology of the Cell:

Biologists distinguish four levels of organization in the structure of a protein. The amino acid sequence is known as the primary structure of the protein. Stretches of polypeptide chain that form α helices and β sheets constitute the protein’s secondary structure. The full three-dimensional organization of a polypeptide chain is sometimes referred to as the protein’s tertiary structure, and if a particular protein molecule is formed as a complex of more than one polypeptide chain, the complete structure is designated as the quaternary structure.

https://www.ncbi.nlm.nih.gov/books/NBK26830/#A406

+/- drdoom(873),


 +4 
submitted by usmle11a(74),
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ok sgyu dan i quoet rofm roeebelm0:tnats4uthe/sa/rit/.if1rtmgtoctsop.o2owccles/ppdeeiwhisw-/s

0%9" ahev na febalniiited cetigne matutino LOC A11 nad LCO 21A
su ceas laoarbnm lnolaceg r-gklsnsnoiic vai a nleygci ubttuisinsto in eth oaorllgepcn meclleuo "

icwhh sname ahtt IO ahs a ycilnge sitnutiutbos nda erehrtfo tis baelun to rmof a coranesyd u.utrerctsu




 +3 
submitted by hungrybox(1025),
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uDe to ey'gcisnl amsll ,ezis ti etraecs kk"sni" ni teh nmiao adci eucseqn.e Tehes kkins aer neddee ot lcyrretoc ormf the yreaoncsd usctr.teru

rehOt awsn:res

  • n"eewdkea tortcnienia ebentwe lecnolag adn oltac"ergnpoy - oncalgel + otarloypgnce = riletla.agc hTe otsuienq smet inmstone ynma fcdtees ni EbNO epty( I llg)aceno tbu no eimotnn of fdecest ni alWaOgeTlcr py(te II lol)necag



 +0 
submitted by an_improved_me(12),

ANother way to get at it is via elimination:

A. hydrogen bonding wouldnt really change since neither alanine nor glycine are polar B. Gly > Ala shouldn't change how proline is modified (I mean it COULD, if there was a steric hindrance or something, but not a great answer) D. nothing to indicate that collagen degredation is altered in response to an AA substitution. Also, in the context of OI (which is the presenting complaint), we already know that the problem doesn't have anything to do with degredation, more with the change in structure/function E. Honestly don't know.




 +0 
submitted by drdoom(873),
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serHe’ noe wya ot mcrlosisei-a-pfontee ecddaseer“ dbohdegnroy-n aot”nfmiro: ’Im ont a ibg naf fo isth niel fo nognar,sei tub ncclielhyta lnaiean as a sdie pourg ahs omre oegs*drnhy orf lettipoan rgdhyone onndibg tnha yicnleg:

ena:ailn 3H—C
ciyl:nge —H

,oS ecl”ni“hcy,tla aialenn wolud etmrip emor hdnb-yndrgoeo afti,omnro hhcwi timgh owlla ouy to niliatmee atht i.choce

hatT is,da ti eemss lsmoat seopibmsli to luer uto t(uhiwot evry ehcanlcti dkwlegone ro smoe orvieddp pmnixtrleeae ata)d tath eth slhglity lerrga inalean soed ton iraimp yrodnghe bnnogid tneeebw aoclgenl luseclmoe iav tirsce ita(s)lpa eeircre.nneft In meslpir s,rtem ncesi aninale si elrrga, uoy loduw inthk htat ti sumt eowsmoh ertnfeeri wthi teh eobhgdnd-gnnryoi ahtt occrus with the dilywtep- gcylnie.

---
cSttlryi* apgiksne, s’ti tno het nubmer fo onsgeyrhd ubt lsoa hte etgnstrh fo het pdeoli atth aecasifltti yhongder noding:b a yenhogdr bduno ot a glotnsry ecreivenetgotal emllueoc ekli fnelioru ilwl “appe”ar more iotsevip dan, s,uht dodrh-ngbnyeo remo rgnsoytl hiwt a enaryb yngexo rcpdeam(o wthi a gyeordnh eocctednn ot o,anrcb orf x)eaempl.

hurFrte daeirn:g

  1. d/.cqdgtlpne/hubopemllshsduuit/:h.uwhtedwwcmhp./.ri/e
hungrybox  Appreciate the effort but this is far too long to be useful. +26  
drachenx  hungrybox is a freaking hater +  
drdoom  @drachenx haha, nah, coming back to this i realize i was probably over-geeking lol +  
blueberrymuffinbabey  isn't the hydrogen bonding dependent on the hydroxylated proline and lysine? so that wouldn't really be the issue here since those aren't the aas being altered? +  
drdoom  @blueberry According to Alberts’ MBoC (see Tangents at right), hydroxylysine and hydroxyproline contribute hydrogen bonds that form between the chains (“interchain”, as opposed to intra-chain; the chains, of course, are separate polypeptides; that is, separate collagen proteins; and interactions between separate chains [separate polypeptides] is what we call “quaternary structure”; see Tangent above). And in this case, as you point out, the stem describes a Gly->Ala substitution. That seems to mean two things: (1) the three separate collagen polypeptides will not “pack [as] tightly” to form the triple helix (=quaternary structure) we all know and love and (2) proline rings will fail to layer quite as snugly, compromising the helical conformation that defines an alpha chain (=secondary structure; the shapes that form within a single polypeptide). +  
tadki38097  also you can't H bond with carbon, it's not polar enough +  

From Molecular Biology of the Cell:

Hydroxylysines and hydroxyprolines are infrequently found in other animal proteins, although hydroxyproline is abundant in some proteins in the plant cell wall. In collagen, the hydroxyl groups of these amino acids are thought to form interchain hydrogen bonds that help stabilize the triple-stranded helix. Conditions that prevent proline hydroxylation, such as a deficiency of ascorbic acid (vitamin C), have serious consequences. (Emphasis mine)

https://www.ncbi.nlm.nih.gov/books/NBK26810/#A3555

+/- drdoom(873),

From Molecular Biology of the Cell:

The primary feature of a typical collagen molecule is its long, stiff, triple-stranded helical structure, in which three collagen polypeptide chains, called α chains, are wound around one another in a ropelike superhelix (Figure 19-43). Collagens are extremely rich in proline and glycine, both of which are important in the formation of the triple-stranded helix. Proline, because of its ring structure, stabilizes the helical conformation in each α chain, while glycine is regularly spaced at every third residue throughout the central region of the α chain. Being the smallest amino acid (having only a hydrogen atom as a side chain), glycine allows the three helical α chains to pack tightly together to form the final collagen superhelix (see Figure 19-43).

https://www.ncbi.nlm.nih.gov/books/NBK26810/#_A3551_

+/- drdoom(873),


 +0 
submitted by nmb29(0),
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I mghit be reinonvtgihk it ,tbu H odnb oamnfirto of as'a kmsea het oecdayrsn rcestrutu fo eht ptierno (nleoagcl in hits )s.cae Teh Gyl to Aal nbsttsouiuit dsoe sturel in essl H obnd itoonf,mar btu fo vidaunliid aas' nto twbneee lonegacl lelocuems ath(t gmhti eb ermo fro rtuearaynq r)ctsueutr

lpp06  I think the key is in the answer phrasing, the answer mentioning H-bonds says "Disruption of H-bonds between collagen molecules" Although collagen does undergo H-bonding to support the triple helix, this is done within the same collagen molecule. Linking different collagen molecules occurs via the lysine - hydroxylysine links done in the ECM +1  
kevin  this is the one comment that finally helped me understand why that was incorrect. thank you +  



 +0 
submitted by basic_pathology(11),

Gly-X-Y is backbone for collagen alpha chain. 3 collagen alpha chains spiral to form triple helix. Glycine has no R group, allowing for flexibility and formation of triple helix. No glycine prevents this continuous spiraling, preventing the formation of collagen secondary structure.

Recall that alpha-helices and beta-sheets are examples of secondary structures. This can be thought of a manifestation of the alpha helix.




 +0 
submitted by j123(8),

Primary structure = amino acid sequence Secondary structure = structure formed with a single amino acid sequence (beta pleated sheet, alpha helix, etc) Tertiary structure = multiple secondary structures interacting together (multiple beta pleated sheets stacked on top of each other, etc) Quarternary structure = protein structure formed from folding of all tertiary structures to make binding sites, etc.

Since the alanine was put in place of the Glycine, the primary structure was unable to form an alpha helix since alpha helix structures need a particular sequence (gly - x- y) in order to form hydrogen bonds to keep the helix stable.




 -4 
submitted by lilmonkey(18),
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Gyl si ao,plr ienaAln is nnooprla dan bcrih.oyodhp eissnsMe envteoocavrnisn ainmt.uot ehTse AsA aveh frntedief aemcchil prstropeie whhic lade ot edupisrtd nripote gfdionl soyaedcn(r )rtuces.tru aimilSr to Gul - Vla sitiusoubtnt ni iklceS lCel .eesDias