Miller Gregory J, Mattera Rafael, Bonifacino Juan S, Hurley James H
Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892, USA.
Nat Struct Biol. 2003 Aug;10(8):599-606. doi: 10.1038/nsb953.
Adaptor proteins load transmembrane protein cargo into transport vesicles and serve as nexuses for the formation of large multiprotein complexes on the nascent vesicles. The gamma-adaptin ear (GAE) domains of the AP-1 adaptor protein complex and the GGA adaptor proteins recruit accessory proteins to these multiprotein complexes by binding to a hydrophobic motif. We determined the structure of the GAE domain of human GGA3 in complex with a peptide based on the DFGPLV sequence of the accessory protein Rabaptin-5 and refined it at a resolution of 2.2 A. The leucine and valine residues of the peptide are partly buried in two contiguous shallow, hydrophobic depressions. The anchoring phenylalanine is buried in a deep pocket formed by the aliphatic portions of two conserved arginine residues, along with an alanine and a proline, illustrating the unusual function of a cluster of basic residues in binding a hydrophobic motif.
衔接蛋白将跨膜蛋白货物装载到运输小泡中，并作为新生小泡上大型多蛋白复合物形成的枢纽。AP-1衔接蛋白复合物和GGA衔接蛋白的γ-衔接蛋白耳（GAE）结构域通过与疏水基序结合，将辅助蛋白招募到这些多蛋白复合物中。我们确定了人GGA3的GAE结构域与基于辅助蛋白Rabaptin-5的DFGPLV序列的肽形成的复合物的结构，并以2.2 Å的分辨率对其进行了优化。该肽的亮氨酸和缬氨酸残基部分埋在两个相邻的浅疏水凹陷中。锚定苯丙氨酸埋在由两个保守精氨酸残基的脂肪族部分以及一个丙氨酸和一个脯氨酸形成的深口袋中，说明了一组碱性残基在结合疏水基序中的独特功能。
