The region(s) of a membrane protein that span the membrane have specific primary

Question

The region(s) of a membrane protein that span the membrane have specific primary and secondary structure properties. Examine the diagram here of the amino acid sequence of the single-span protein nerve growth factor receptor, or NGF receptor. This is a simple primary structure (amino acid sequence), with the residues numbered N-terminus to c-terminus, from 1 to 796. The numbering system is simple: the zero in "10" sits directly above the single-letter abbreviation for the 10th residue, the zero in "20" sits above the 20th residue, etc. There are three different 20-residue sequences highlighted (in red, green and blue) that are possible membrane spans. Which do you think is most likely to be the correct one?

Explanation / Answer

The correct answer is blue.

Explanation:

The lipid bilayer is the basic structure of the plasma membrane. The bilayer is composed of mainly phospholipid molecules, whose polar head groups are in contact with the intra- or extracellular aqueous phase. The hydrophobic (non-polar) fatty acid tails of phospholipids face each other, and constitute the hydrophobic interior of the membrane.

This nerve growth factor or NGF receptor is a single-span transmembrane protein. The membrane-spanning region of transmembrane protein contains mainly hydrophobic amino acid residues and almost none of them are charged.

The red amino acid sequence:

Lys(K)-Cys(C)-Gly(G)-Arg(R)-Arg(R)-Asn(N)-Lys(K)-Phe(F)-Gly(G)-Ile(I)-Asn(N)-Arg(R)-Pro(P)-Ala(A)-Val(V)-Leu(L)-Ala(A)-Pro(P)-Glu(E)-Asp(D)

This sequence contains 10 hydrophobic amino acid residues out of 20.

The blue amino acid sequence:

Val(V)-Ala(A)-Val(V)-Gly(G)-Leu(L)-Ala(A)-Val(V)-Phe(F)-Ala(A)-Cys(C)-Leu(L)-Phe(F)-Leu(L)-Ser(S)-Thr(T)-Leu(L)-Leu(L)-Leu(L)-Val(V)-Leu(L)

This sequence contains 17 hydrophobic amino acid residues out of 20 and all of the 20 amino acid residues are uncharged.

The green amino acid sequence:

Pro(P)-Asn(N)-Ala(A)-Ser(S)-Val(V)-Asp(D)-Val(V)-Gly(G)-Asp(D)-Asp(D)-Val(V)-Leu(L)-Leu(L)-Arg(R)-Cys(C)-Gln(Q)-Val(V)-Glu(E)-Gly(G)-Arg(R)

This sequence contains 10 hydrophobic amino acid residues out of 20.

Therefore the blue amino acid sequence is most likely to be the membrane span.

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