Shan Shu-ou, Walter Peter
Howard Hughes Medical Institute, Department of Biochemistry and Biophysics, University of California, San Francisco, USA.
FEBS Lett. 2005 Feb 7;579(4):921-6. doi: 10.1016/j.febslet.2004.11.049.
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.
信号识别颗粒（SRP）介导新生蛋白质共翻译靶向至真核生物内质网膜或细菌质膜。在此过程中，两个GTP酶，一个在SRP中，另一个在SRP受体（SR）中，形成一个复合物，其中两种蛋白质相互激活彼此的GTP酶反应。嗜热水生菌SRP.SR复合物的最新晶体结构表明，这两个GTP酶通过一个异常广泛且高度协同的相互作用表面结合，并在界面处形成一个复合活性位点。GTP酶激活通过一种独特机制进行，该机制受到跨二聚体界面的两个GTP分子之间的相互作用以及构象重排的刺激，这些构象重排使每个活性位点中的催化残基相对于结合的底物定位。已分离出不同类别的突变，这些突变抑制SRP - SR复合物形成和激活过程中的特定阶段，表明活性SRP.SR复合物形成过程中存在离散的构象阶段。每个阶段在靶向反应中提供一个潜在的控制点，在该点可以施加其他组分的调节作用，从而确保货物在适当时间的结合和释放。
