SecA: Difference between revisions

{{ STRUCTURE_3jv2 | PDB=3jv2 | SCENE=Sandbox_158/Scene_1/1 }}

[http://www.nature.com/nature/journal/v455/n7215/full/nature07335.html SecA] SecA consists of two RecA-like nucleotide-binding domains (NBD1 and NBD2), which bind the nucleotide between them, a polypeptide-cross-linking domain (PPXD), a helical scaffold domain (HSD) and a helical wing domain (HWD)14. Although several crystal structures of isolated SecA have been determined, the function of the different domains and the mechanism by which SecA moves polypeptides through the channel remain unknown. Disulphide cross-linking experiments suggest that SecA binds by its NBD1 domain to a non-translocating SecY copy, and moves the polypeptide chain through a neighbouring SecY molecule6. These and other experiments indicate that SecA functions as a monomer during translocation7, 15, 16, 17, but the issue remains controversial18, 19, 20.

Here we report crystal structures of SecA bound in an intermediate state of nucleotide hydrolysis to the SecY channel. The structures suggest mechanisms for how the channel is opened and prepared for the arrival of a translocation substrate, and how SecA moves polypeptides through the channel. http://www.nature.com/nature/journal/v455/n7215/full/nature07335.html

[http://journal.shouxi.net/qikan/article.php?id=418668 SecA] SecA interacts not only with the SecY channel (8) but also with acidic phospholipids (9-11) and with both the signal sequence and the mature part of a substrate protein (12). It also binds the chaperone SecB, which ushers some precursor proteins to SecA (8, 13, 14). When associated with the SecY complex, SecA undergoes repeated cycles of ATP-dependent conformational changes, which are linked to the movement of successive segments of a polypeptide chain through the channel (15, 16). However the mechanism employed by SecA to translocate substrates polypeptide chains through the SecY channel remains largely unknown.

An important issue concerning the function of SecA is its oligomeric state during translocation. SecA is a dimer in solution (17, 18), and previous work argued that this is its functional state (19). An x-ray structure of Bacillus subtilis SecA also indicates the existence of a dimer (7). However, recent evidence raises the possibility that SecA might actually function as a monomer; in solution, SecA dimers are in rapid equilibrium with monomers (20, 21). Although the equilibrium favors dimers, it is shifted almost completely toward monomers in the presence of membranes containing acidic phospholipids or upon binding to the SecY complex (21). A synthetic signal peptide had a similar effect, although this result is controversial (22). A monomeric derivative of SecA containing six point mutations retained some in vitro translocation activity (21), but the low level of translocation precluded any firm conclusion. In addition, the previous results do not exclude models in which SecA cycles between monomeric and oligomeric states during the translocation of a polypeptide chain (22, 23). Most importantly, the functional oligomeric state of SecA in vivo remains to be established. http://journal.shouxi.net/qikan/article.php?id=418668