Structural basis for endosomal trafficking of diverse transmembrane cargos by PX-FERM proteins

作者：Ghai Rajesh; Bugarcic Andrea; Liu Huadong; Norwood Suzanne J; Skeldal Sune; Coulson Elizabeth J; Li Shawn Shun Cheng; Teasdale Rohan D; Collins Brett M^*

来源：Proceedings of the National Academy of Sciences, 2013, 110(8): E643-E652.

DOI：10.1073/pnas.1216229110

• endosome
• protein crystallography
• X-ray scattering
• membrane trafficking

Transit of proteins through the endosomal organelle following endocytosis is critical for regulating the homeostasis of cell-surface proteins and controlling signal transduction pathways. However, the mechanisms that control these membrane-transport processes are poorly understood. The Phox-homology (PX) domain-containing proteins sorting nexin (SNX) 17, SNX27, and SNX31 have emerged recently as key regulators of endosomal recycling and bind conserved Asn-Pro-Xaa-Tyr-sorting signals in transmembrane cargos via an atypical band, 4.1/ezrin/radixin/moesin (FERM) domain. Here we present the crystal structure of the SNX17 FERM domain bound to the sorting motif of the P-selectin adhesion protein, revealing both the architecture of the atypical FERM domain and the molecular basis for recognition of these essential sorting sequences. We further show that the PX-FERM proteins share a promiscuous ability to bind a wide array of putative cargo molecules, including receptor tyrosine kinases, and propose a model for their coordinated molecular interactions with membrane, cargo, and regulatory proteins.

• 出版日期2013-2-19