CELL: Yan Ning group discovers the structural basis of genetic neuropathy in children
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Last Update: 2020-06-21
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Source: Internet
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Author: User
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The release ofcholesterolin the lysosome stakes requires two proteins, NPC1 and NPC2, whose defects are responsible for Niemann-Pick's disease Type C (NPC)Recently, yanning team proposed the structural representation of NPC1 and NPC2 systems, revealing the molecular basis of the low pH-dependent transmembrane (TM) domain of cholesterol transfer from NPC2 to NPC1at pH 8.0, the structure of NPC1 with resolutions of 3.6 and 3.0 , respectively, is obtained in nanodiscs and detergents, which are very similar, revealing the tunnels connecting the N-end domain (NTD) and trans-diasterol sensing domain (SSD)at pH 5.5, NTD exhibits two conformations that indicate the movement of cholesterol to the tunnelA hypothetical cholesterol molecule was found at the membrane boundary of the tunnel, and TM2 moved toward the formation of surface pockets on the SSDfinally, under pH5.5, the researchers obtained a 4.0-resolution NPC1-NPC2 composite structure that clarified the molecular basis of cholesterol delivery from NPC2 to NPC1 (NTD)
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