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Structure of SCARB2-JL2 complex
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 PubMedEntero virus 71 (EV71) causes hand, foot, and mouth disease (HFMD) and occasionally leads to severe neurological complications and even death. Scavenger receptor class B member 2 (SCARB2) is a functional receptor for EV71, that mediates viral attachment, internalization, and uncoating. However, the exact binding site of EV71 on SCARB2 is unknown. In this study, we generated a monoclonal antibody (mAb) that binds to human but not mouse SCARB2. It is named JL2, and it can effectively inhibit EV71 infection of target cells. Using a set of chimeras of human and mouse SCARB2, we identified that the region containing residues 77-113 of human SCARB2 contributes significantly to JL2 binding. The structure of the SCARB2-JL2 complex revealed that JL2 binds to the apical region of SCARB2 involving alpha-helices 2, 5, and 14. Our results provide new insights into the potential binding sites for EV71 on SCARB2 and the molecular mechanism of EV71 entry. The binding of a monoclonal antibody to the apical region of SCARB2 blocks EV71 infection.,Zhang X, Yang P, Wang N, Zhang J, Li J, Guo H, Yin X, Rao Z, Wang X, Zhang L Protein Cell. 2017 Aug;8(8):590-600. doi: 10.1007/s13238-017-0405-7. Epub 2017, Apr 26. PMID:28447294[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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