4tw0 | pdb_00004tw0
Crystal Structure of SCARB2 in Acidic Condition (pH4.8)
Structural highlights
DiseaseSCRB2_HUMAN Unverricht-Lundborg disease;Gaucher disease type 1;Action myoclonus - renal failure syndrome. The disease is caused by mutations affecting the gene represented in this entry. Genetic variants in SCARB2 can act as modifier of the phenotypic expression and severity of Gaucher disease. FunctionSCRB2_HUMAN Acts as a lysosomal receptor for glucosylceramidase (GBA) targeting.[1] Publication Abstract from PubMedUnlike the well-established picture for the entry of enveloped viruses, the mechanism of cellular entry of non-enveloped eukaryotic viruses remains largely mysterious. Picornaviruses are representative models for such viruses, and initiate this entry process by their functional receptors. Here we present the structural and functional studies of SCARB2, a functional receptor of the important human enterovirus 71 (EV71). SCARB2 is responsible for attachment as well as uncoating of EV71. Differences in the structures of SCARB2 under neutral and acidic conditions reveal that SCARB2 undergoes a pivotal pH-dependent conformational change which opens a lipid-transfer tunnel to mediate the expulsion of a hydrophobic pocket factor from the virion, a pre-requisite for uncoating. We have also identified the key residues essential for attachment to SCARB2, identifying the canyon region of EV71 as mediating the receptor interaction. Together these results provide a clear understanding of cellular attachment and initiation of uncoating for enteroviruses. Molecular mechanism of SCARB2-mediated attachment and uncoating of EV71.,Dang M, Wang X, Wang Q, Wang Y, Lin J, Sun Y, Li X, Zhang L, Lou Z, Wang J, Rao Z Protein Cell. 2014 Sep;5(9):692-703. doi: 10.1007/s13238-014-0087-3. Epub 2014, Jul 2. PMID:24986489[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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