Thursday, September 27, 2007

Human Genes Involved in the Signal Hypothesis Pathway

 
The Signal Hypothesis describes the mechanism whereby proteins that are destined to cross a membrane are synthesized. One of the key components of this pathway is Signal Recognition Particle or SRP. The structure of SRP is shown below from a paper by Maity and Weeks (2007)

Most of SRP is composed of an RNA molecule called 7SL RNA. It is shown as red and yellow helices in the bottom figure. The secondary structure is depicted in the top right-hand corner of the figure. There are six different proteins in SRP. All of them are bound to the RNA in one way or another. The six proteins are SRP9, SRP14, SRP54, SRP68, and SRP72. The numbers refer to the molecular mass in kilodaltons.


There are three genes for 7SL RNA. They are all found on chromosome 14 (above). Two of them are closely linked and the third one is somewhat farther away.

The genes for the protein components are:

The three membrane components are the SRP receptor, the translocon (formerly known as ribophorin), and the signal peptidase. There are two subunits in the SRP receptor, α (docking protein) and β. The human genome contains a single gene for SRP receptor α subunit called SSPR (SSPRα). The genome has two separate genes for the β subunit called SSRB and SSR2.

The translocon is composed of three proteins; SEC61, SEC62, and SEC63. The SEC61 protein has three subunits; α (genes SEC61A1 and SEC61A2), β (gene SEC61B), and γ (gene SEC61G).

Finally, there are three subunits of the signal peptidase complex encoded by SPCS1 (signal peptidase complex, subunit 1), SPCS2, and SPCS3.

There are 20 genes required for effective translocation of proteins with a signal sequence (only the SRP are shown on the chromosome maps). Additional proteins are required to assist in the translocation (chaperones) and in glycosylation of the protein once it enters the lumen of the endoplasmic reticulum.


Maity, T.S. and Weeks, K.M. (2007) A threefold RNA-protein interface in the signal recognition particle gates native complex assembly. J. Mol. Biol. 369:512-24 [PubMed]

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