Molecular switches involving the AP-2 β2 appendage regulate endocytic cargo selection and clathrin coat assembly
Molecular switches involving the AP-2 β2 appendage regulate endocytic cargo selection and clathrin coat assembly
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DOI：
10.1016/j.devcel.2006.01.016
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发表时间：
2006-03-01
影响因子：
11.8
通讯作者：
Traub, LM
中科院分区：
文献类型：
--
作者：
Edeling, MA;Mishra, SK;Traub, LM
网格蛋白相关的分选蛋白（CLASPs）扩展了被网格蛋白包裹的囊泡中的内吞货物的种类，超出了与AP-2接头物理结合的跨膜蛋白。LDL和gpcr分别被ARH和β -抑制素内化。我们发现这两个CLASPs通过α -螺旋[DE](n)X1-2FXX[FL]XXXR基序选择性地结合到AP-2 β 2附体平台上，并且该基序也出现在epsin中并起作用。在β -抑制蛋白中，该基序通过以β链构象结合回蛋白质的折叠核心来维持内吞不能力状态。通过β -抑制蛋白/GPCR相互作用触发，基序必须移位，并且必须经历链到螺旋的转变，以使β 2附体结合，从而驱动GPCR- β -抑制蛋白复合物进入网格蛋白外壳。在β 2附体夹层上发现了eps15和网格蛋白等蛋白质的另一个相互作用表面，这表明在组装过程中，网格蛋白将eps15置换到晶格边缘的机制。
Clathrin-associated sorting proteins (CLASPs) expand the repertoire of endocytic cargo sorted into clathrin-coated vesicles beyond the transmembrane proteins that bind physically to the AP-2 adaptor. LDL and GPCRs are internalized by ARH and beta-arrestin, respectively. We show that these two CLASPs bind selectively to the AP-2 beta 2 appendage platform via an alpha-helical [DE](n)X1-2FXX[FL]XXXR motif, and that this motif also occurs and is functional in the epsins. In beta-arrestin, this motif maintains the endocytosis-incompetent state by binding back on the folded core of the protein in a beta strand conformation. Triggered via a beta-arrestin/GPCR interaction, the motif must be displaced and must undergo a strand to helix transition to enable the beta 2 appendage binding that drives GPCR-beta-arrestin complexes into clathrin coats. Another interaction surface on the beta 2 appendage sandwich is identified for proteins such as eps15 and clathrin, suggesting a mechanism by which clathrin displaces eps15 to lattice edges during assembly.