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Co‐translational protein targeting by the signal recognition particle
Author(s) -
Shan Shu-ou,
Walter Peter
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2004.11.049
Subject(s) - gtpase , signal recognition particle , signal recognition particle receptor , endoplasmic reticulum , biophysics , dimer , chemistry , microbiology and biotechnology , conformational change , biology , membrane , protein targeting , biochemistry , membrane protein , peptide sequence , signal peptide , organic chemistry , gene
The signal recognition particle (SRP) mediates the co‐translational targeting of nascent proteins to the eukaryotic endoplasmic reticulum membrane, or the bacterial plasma membrane. During this process, two GTPases, one in the SRP and one in the SRP receptor (SR), form a complex in which both proteins reciprocally activate the GTPase reaction of one another. The recent crystal structures of the T. aquaticus SRP · SR complex show that the two GTPases associate via an unusually extensive and highly cooperative interaction surface, and form a composite active site at the interface. GTPase activation proceeds through a unique mechanism, stimulated by both interactions between the twinned GTP molecules across the dimer interface and by conformational rearrangements that position catalytic residues in each active site with respect to the bound substrates. Distinct classes of mutations have been isolated that inhibit specific stages during SRP–SR complex formation and activation, suggesting discrete conformational stages during formation of the active SRP · SR complex. Each stage provides a potential control point in the targeting reaction at which regulation by additional components can be exerted, thus ensuring the binding and release of cargo at the appropriate time.