3wsy

SorLA Vps10p domain in complex with its own propeptide fragment

spinqualitylabelsall models 3wsy, resolution 3.11Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3wsy is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.11Å Ligands: NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function SORL_HUMAN Likely to be a multifunctional endocytic receptor, that may be implicated in the uptake of lipoproteins and of proteases. Binds LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. Binds the receptor-associated protein (RAP). Could play a role in cell-cell interaction. Publication Abstract from PubMed SorLA is a neuronal sorting receptor considered to be a major risk factor for Alzheimer's disease. We have recently reported that it directs lysosomal targeting of nascent neurotoxic amyloid-beta (Abeta) peptides by directly binding Abeta. Here, we determined the crystal structure of the human sorLA domain responsible for Abeta capture, Vps10p, in an unbound state and in complex with two ligands. Vps10p assumes a ten-bladed beta-propeller fold with a large tunnel at the center. An internal ligand derived from the sorLA propeptide bound inside the tunnel to extend the beta-sheet of one of the propeller blades. The structure of the sorLA Vps10p-Abeta complex revealed that the same site is used. Peptides are recognized by sorLA Vps10p in redundant modes without strict dependence on a particular amino acid sequence, thus suggesting a broad specificity toward peptides with a propensity for beta-sheet formation. Structural basis for amyloidogenic peptide recognition by sorLA.,Kitago Y, Nagae M, Nakata Z, Yagi-Utsumi M, Takagi-Niidome S, Mihara E, Nogi T, Kato K, Takagi J Nat Struct Mol Biol. 2015 Mar;22(3):199-206. doi: 10.1038/nsmb.2954. Epub 2015, Feb 2. PMID:25643321 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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