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10.7554/eLife.57089 http://scihub22266oqcxt.onion/10.7554/eLife.57089 32410728!7228765!32410728     free     free     free Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Elife 2020 ; 9 (ä): ä Nephropedia Template TP {{tp|p=32410728|t=2020. Inter-domain dynamics drive cholesterol transport by NPC1 and NPC1L1 proteins |pdf=|usr=}}{{32410728}} gab.com Text Inter-domain dynamics drive cholesterol transport by NPC1 and NPC1L1 proteins JO: Elife http://www.kidney.de/pget.php?&tw=1&pmid=32410728 #FOAvip Transport of LDL-derived cholesterol from lysosomes into the cytoplasm requires NPC1 protein; NPC1L1 mediates uptake of dietary cholesterol. We introduced single disulfide bonds into NPC1 and NPC1L1 to explore the importance of inter-domain dynamics in cholesterol transport. Using a sensitive method to monitor lysosomal cholesterol efflux, we found that NPC1's N-terminal domain need not release from the rest of the protein for efficient cholesterol export. Either introducing single disulfide bonds to constrain lumenal/extracellular domains or shortening a cytoplasmic loop abolishes transport activity by both NPC1 and NPC1L1. The widely prescribed cholesterol uptake inhibitor, ezetimibe, blocks NPC1L1; we show that residues that lie at the interface between NPC1L1's three extracellular domains comprise the drug's binding site. These data support a model in which cholesterol passes through the cores of NPC1/NPC1L1 proteins; concerted movement of various domains is needed for transfer and ezetimibe blocks transport by binding to multiple domains simultaneously. Twit Text FOAVip Inter-domain dynamics drive cholesterol transport by NPC1 and NPC1L1 proteins ????Elife http://www.kidney.de/pget.php?&tw=1&pmid=32410728 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=32410728 #FOAvip English Wikipedia <ref>{{Cite pmid|32410728}}</ref> Inter-domain dynamics drive cholesterol transport by NPC1 and NPC1L1 proteins #MMPMID32410728 Saha P; Shumate JL; Caldwell JG; Elghobashi-Meinhardt N; Lu A; Zhang L; Olsson NE; Elias JE; Pfeffer SR Elife 2020[May]; 9 (ä): ä PMID32410728show ga Transport of LDL-derived cholesterol from lysosomes into the cytoplasm requires NPC1 protein; NPC1L1 mediates uptake of dietary cholesterol. We introduced single disulfide bonds into NPC1 and NPC1L1 to explore the importance of inter-domain dynamics in cholesterol transport. Using a sensitive method to monitor lysosomal cholesterol efflux, we found that NPC1's N-terminal domain need not release from the rest of the protein for efficient cholesterol export. Either introducing single disulfide bonds to constrain lumenal/extracellular domains or shortening a cytoplasmic loop abolishes transport activity by both NPC1 and NPC1L1. The widely prescribed cholesterol uptake inhibitor, ezetimibe, blocks NPC1L1; we show that residues that lie at the interface between NPC1L1's three extracellular domains comprise the drug's binding site. These data support a model in which cholesterol passes through the cores of NPC1/NPC1L1 proteins; concerted movement of various domains is needed for transfer and ezetimibe blocks transport by binding to multiple domains simultaneously. |Animals[MESH] |Anticholesteremic Agents/pharmacology[MESH] |Biological Transport[MESH] |Cholesterol/*metabolism[MESH] |Ezetimibe/pharmacology[MESH] |HEK293 Cells[MESH] |HeLa Cells[MESH] |Humans[MESH] |Intracellular Signaling Peptides and Proteins/chemistry/genetics/*metabolism[MESH] |Lysosomes/drug effects/*metabolism[MESH] |Membrane Transport Proteins/chemistry/drug effects/genetics/*metabolism[MESH] |Molecular Dynamics Simulation[MESH] |Niemann-Pick C1 Protein/chemistry/genetics/*metabolism[MESH] |Protein Domains[MESH] |Sf9 Cells[MESH]Inter-domain dynamics drive cholesterol transport by NPC1 and NPC1L1 p(epmc).pdf DeepDyve Pubget Overpricing