Misura K M, Scheller R H, Weis W I
Department of Structural Biology, Stanford University School of Medicine, California 94305, USA.
Nature. 2000 Mar 23;404(6776):355-62. doi: 10.1038/35006120.
Syntaxin 1a and neuronal Sec1 (nSec1) form an evolutionarily conserved heterodimer that is essential for vesicle trafficking and membrane fusion. The crystal structure of the nSec1-syntaxin 1a complex, determined at 2.6 A resolution, reveals that major conformational rearrangements occur in syntaxin relative to both the core SNARE complex and isolated syntaxin. We identify regions of the two proteins that seem to determine the binding specificity of particular Sec1 proteins for syntaxin isoforms, which is likely to be important for the fidelity of membrane trafficking. The structure also indicates mechanisms that might couple the action of upstream effector proteins to conformational changes in syntaxin 1a and nSec1 that lead to core complex formation and membrane fusion.
syntaxin 1a与神经元Sec1(nSec1)形成一种进化上保守的异二聚体,这对于囊泡运输和膜融合至关重要。以2.6埃分辨率测定的nSec1-syntaxin 1a复合物的晶体结构表明,相对于核心SNARE复合物和分离的syntaxin,syntaxin发生了主要的构象重排。我们确定了这两种蛋白质的区域,这些区域似乎决定了特定Sec1蛋白对syntaxin亚型的结合特异性,这可能对膜运输的保真度很重要。该结构还表明了可能将上游效应蛋白的作用与syntaxin 1a和nSec1的构象变化相耦合的机制,这些构象变化导致核心复合物形成和膜融合。