Question

Describe the insertion of type I, II, III and IV into the ER membrane? Differences?

Answer 1

The difference between the four classes of proteins (structural and functional difference) is determined by the topology with which their peptide backbone aligns with the phospholipids bilayer. The topology is in turn dictated by the insertion orientation of the transmembrane segment, and the N-terminus which can either be cytoplasmic or it can be exofacial.

Type-1 proteins exhibit the presence of a cleavable signal at their N-terminus. The SRP (signal recognition particle) binds to this cleavable signal and then directs the nascent polypeptide to the Endoplasmic reticulum (ER), where further signal functions helps in the transfer of mature N-terminus of the protein across the ER membrane. In order for the protein to adopt an exofacial topology, there is a second hydrophobic domain which acts as an anchor.

Type-2 proteins exhibit the presence of an uncleavable signal/anchor domain, but they adopt a cytoplasmic N-teminus topology during insertion.

Type- 3 proteins also exhibit the presence of an uncleavable signal/anchor domain. They, however, they adopt a exofacial N-teminus topology during insertion.

All the above three classes of proteins use a Sec machinery for insertion into the ER.

Type-4 proteins exhibit a carboxyl terminal signal/anchor domain, and they seem to adopt a cytoplasmic topology during insertion. However, they employ a different mechanism for entry into the ER , as compared to Types 1,2,and 3.