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NBME 21 Answers

 +58  upvote downvote
submitted by โˆ—drdoom(1202)

The synthesis of virtually all proteins (mRNA->peptide) occurs in the cytoplasm.[1] Thatโ€™s where all ribosomes reside, after all. Ribosomes, which are mostly just rRNA (~2/3 rRNA + 1/3 protein*, by weight), are assembled in the nucleus but only do their stuff once they get to the cytoplasm.

For a protein to leave its original hometown of the cytosol and become a resident of the nucleus or, sayyyyyy, the endoplasmic reticulum, it needs to have a little string of amino acids which shout โ€œI belong in the nucleus!โ€ or โ€œI belong in the endoplasmic reticulum!โ€

Proteins ultimately destined for the ER contain an unimaginatively named string of amino acids known as โ€œsignal sequence,โ€ which, for the purposes of the Step 1, is always at the N-terminus. The signal sequence tells other cytosolic proteins, โ€œHey! Take me (and the rest of the peptide of which I am part) to the ER!โ€

In the absence of this signal, a protein will remain in its โ€œdefaultโ€ home of the cytosol.

Here’s a nice schematic showing the flow of proteins from initial synthesis to final destinations:


  1. โ€œThe synthesis of virtually all proteins in the cell begins on ribosomes in the cytosol.โ€ (Essential Cell Biology, Alberts et al., 2014, p. 492)

*If you really want your mind blown, consider that even the protein subunits that make up that 1/3 of a ribosome are themselves initially synthesized in the cytosol; later, they are transported back into the nucleus via the nuclear pore.

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qball  Awesome explanation. Now explain it to me like I'm 5. +13
drdoom  All baby peptides are born in the cytosol. But some baby peptides have a birthmark at their N-terminus. The birthmark tells a special mailman that this baby needs to be delivered somewhere else. If you chop off the birthmark โ€” or erase it somehow โ€” the mailman never knows to take baby to its true home. The end. Now go to sleep or Santa wonโ€™t bring your presents. +82

 +11  upvote downvote
submitted by โˆ—jejunumjedi(30)

I think this is describing a signal peptide (hydrophobic at N-terminus). Without signal peptide => canโ€™t be transported into endoplasmic reticulum.

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youssefa  Is this even in FA? Biochem chapter only mentions SRPs. +1
lovebug  @youssefa FA19, pg 47.[cell trafficking] but not details... +1

 +3  upvote downvote
submitted by baengotti(3)

The N-terminus is where you have signal peptides which define the target of the proteins (think of them as postal code). Typically, proteins are in the cytoplasm after they are made, but since the have tags at n-terminus, they go to different targets like this case ER. Now, if the protein is retained in the cytoplasm, this means the mutation disabled the tag (no postal code). Hence, it is kept in the cytoplasm.

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minion7  jus a reminder........ I cell disease - mannose residues are to be tagged by phosphate to enter lysosomes - failure of phosphorylation in golgi due to absence of phosphotransferase - proteins are secreted extracellularly but not to lysosomes therefore any protein formed will b tagged before it enters any specific organalle!!! +4
michsmith49  N-Terminus assists with Navigation. N = Navigation. +

 +0  upvote downvote
submitted by โˆ—sd22(2)

Can anyone help explain what the other options would entail?

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