3f6k
From Proteopedia
Crystal structure of the Vps10p domain of human sortilin/NTS3 in complex with neurotensin
Structural highlights
Disease[SORT_HUMAN] Note=A common polymorphism located in a non-coding region between CELSR2 and PSRC1 alters a CEBP transcription factor binding site and is responsible for changes in hepatic expression of SORT1. Altered SORT1 expression in liver affects low density lipoprotein cholesterol levels in plasma and is associated with susceptibility to myocardial infarction. Function[SORT_HUMAN] Functions as a sorting receptor in the Golgi compartment and as a clearance receptor on the cell surface. Required for protein transport from the Golgi apparatus to the lysosomes by a pathway that is independent of the mannose-6-phosphate receptor (M6PR). Also required for protein transport from the Golgi apparatus to the endosomes. Promotes neuronal apoptosis by mediating endocytosis of the proapoptotic precursor forms of BDNF (proBDNF) and NGFB (proNGFB). Also acts as a receptor for neurotensin. May promote mineralization of the extracellular matrix during osteogenic differentiation by scavenging extracellular LPL. Probably required in adipocytes for the formation of specialized storage vesicles containing the glucose transporter SLC2A4/GLUT4 (GLUT4 storage vesicles, or GSVs). These vesicles provide a stable pool of SLC2A4 and confer increased responsiveness to insulin. May also mediate transport from the endoplasmic reticulum to the Golgi.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [NEUT_HUMAN] Neurotensin may play an endocrine or paracrine role in the regulation of fat metabolism. It causes contraction of smooth muscle. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe structure of the Sortilin ectodomain in complex with neurotensin has been determined at 2-A resolution, revealing that the C-terminal part of neurotensin binds in the tunnel of a ten-bladed beta-propeller domain. Binding competition studies suggest that additional binding sites, for example, for the prodomain of nerve growth factor-beta, are present in the tunnel and that competition for binding relates to the restricted space inside the propeller. Ligands bind to Sortilin in the tunnel of a ten-bladed beta-propeller domain.,Quistgaard EM, Madsen P, Groftehauge MK, Nissen P, Petersen CM, Thirup SS Nat Struct Mol Biol. 2009 Jan;16(1):96-8. Epub 2009 Jan 4. PMID:19122660[11] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Human | Groftehauge, M K | Madsen, P | Nissen, P | Petersen, C M | Quistgaard, E M | Thirup, S | 10-bladed beta-propeller | Cys-rich domain | Cytoplasmic vesicle | Developmental protein | Differentiation | Endocytosis | Endoplasmic reticulum | Endosome | Glycoprotein | Golgi apparatus | Lysosome | Membrane | Phosphoprotein | Protein sorting receptor | Protein-peptide complex | Receptor | Secreted | Signaling protein | Sortilin vps10p-d | Ssortilin | Transmembrane | Transport
