Structural basis of Vps33A recruitment to the human HOPS complex by Vps16
Structural basis of Vps33A recruitment to the human HOPS complex by Vps16
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DOI：
10.1073/pnas.1307074110
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发表时间：
2013-08-13
影响因子：
11.1
通讯作者：
Owen, David J.
中科院分区：
文献类型：
--
作者：
Graham, Stephen C.;Wartosch, Lena;Owen, David J.
哺乳动物晚期内溶体和自噬体与溶酶体融合需要多亚基同型融合和液泡蛋白分选（HOPS）膜系固复合体。我们已经确定了人类HOPS亚基Vps33A的晶体结构，确认了其作为Sec1/Munc18家族成员的身份。我们发现，HOPS亚基Vps16将Vps33A招募到人类HOPS复合物中，并且残基642-736对于这种相互作用是必要和充分的，并且我们展示了Vps33A与Vps16复合物的晶体结构（642-736）。结合界面的突变破坏了Vps33A- vps16在体外和细胞中的相互作用，阻止Vps33A向HOPS复合物募集。Vps33A-Vps16复合体为研究Sec1/Munc18蛋白与系固复合物之间的关联提供了一个结构框架。
The multisubunit homotypic fusion and vacuole protein sorting (HOPS) membrane-tethering complex is required for late endosome-lysosome and autophagosome-lysosome fusion in mammals. We have determined the crystal structure of the human HOPS subunit Vps33A, confirming its identity as a Sec1/Munc18 family member. We show that HOPS subunit Vps16 recruits Vps33A to the human HOPS complex and that residues 642-736 are necessary and sufficient for this interaction, and we present the crystal structure of Vps33A in complex with Vps16(642-736). Mutations at the binding interface disrupt the Vps33A-Vps16 interaction both in vitro and in cells, preventing recruitment of Vps33A to the HOPS complex. The Vps33A-Vps16 complex provides a structural framework for studying the association between Sec1/Munc18 proteins and tethering complexes.