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From Proteopedia
Crystal Structure of SNX11/SNX10-PXe Chimera
Structural highlights
DiseaseSNX10_HUMAN Autosomal recessive malignant osteopetrosis. The disease is caused by mutations affecting the gene represented in this entry.[1] [2] [3] FunctionSNX11_HUMAN May be involved in several stages of intracellular trafficking (By similarity).SNX10_HUMAN Probable phosphoinositide-binding protein involved in protein sorting and membrane trafficking in endosomes. Plays a role in cilium biogenesis through regulation of the transport and the localization of proteins to the cilium. Required for the localization to the cilium of V-ATPase subunit ATP6V1D and ATP6V0D1, and RAB8A. Involved in osteoclast differentiation and therefore bone resorption.[4] [5] [6] Publication Abstract from PubMedPhosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) is an essential phosphoinositide required for endosome homeostasis and sorting for lysosomal degradation; however, the underlying mechanisms, especially in mammals, remain elusive or unexplored. Here we determined a structure of PI(3,5)P2 bound to Sorting Nexin 11 (SNX11) with an opened PPII-C loop. We also obtained an SNX11 structure with its PPII-C in "closed" form that serves as a potential PI3P-binding model. In addition, our results reveal that SNX11 can interact with the V1D subunit of vacuolar H(+)-ATPase (V-ATPase), which provides a link between PI(3,5)P2 and human V-ATPase and further evidence for their roles in the endosome homeostasis regulation. Lastly, a new apo-form structure of SNX11, combined with molecular dynamics (MD) studies, indicates that the alpha5 helix can unfold from the PX domain of SNX11 when targeting the membrane or interacting with its partner. Taken together, these findings identify a novel PI(3,5)P2 effector, which will shed light on the PIs recognizing mechanism and the understanding of the downstream sorting events triggered by different PI binding. Molecular Basis for PI(3,5)P2 Recognition by SNX11, a Protein Involved in Lysosomal Degradation and Endosome Homeostasis Regulation.,Xu T, Gan Q, Wu B, Yin M, Xu J, Shu X, Liu J J Mol Biol. 2020 Jun 16. pii: S0022-2836(20)30406-X. doi:, 10.1016/j.jmb.2020.06.010. PMID:32561432[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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