Structures of SALSA/DMBT1 SRCR domains reveal the conserved ligand-binding mechanism of the ancient SRCR fold.

Autor:	Reichhardt MP; Sir William Dunn School of Pathology, University of Oxford, Oxford, UK martinpreichhardt@gmail.com., Loimaranta V; Institute of Dentistry, University of Turku, Turku, Finland., Lea SM; Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.; Central Oxford Structural Molecular Imaging Centre, University of Oxford, Oxford, UK., Johnson S; Sir William Dunn School of Pathology, University of Oxford, Oxford, UK steven.johnson@path.ox.ac.uk.
Jazyk:	angličtina
Zdroj:	Life science alliance [Life Sci Alliance] 2020 Feb 25; Vol. 3 (4). Date of Electronic Publication: 2020 Feb 25 (Print Publication: 2020).
DOI:	10.26508/lsa.201900502
Abstrakt:	The scavenger receptor cysteine-rich (SRCR) family of proteins comprises more than 20 membrane-associated and secreted molecules. Characterised by the presence of one or more copies of the ∼110 amino-acid SRCR domain, this class of proteins have widespread functions as antimicrobial molecules, scavenger receptors, and signalling receptors. Despite the high level of structural conservation of SRCR domains, no unifying mechanism for ligand interaction has been described. The SRCR protein SALSA, also known as DMBT1/gp340, is a key player in mucosal immunology. Based on detailed structural data of SALSA SRCR domains 1 and 8, we here reveal a novel universal ligand-binding mechanism for SALSA ligands. The binding interface incorporates a dual cation-binding site, which is highly conserved across the SRCR superfamily. Along with the well-described cation dependency on most SRCR domain-ligand interactions, our data suggest that the binding mechanism described for the SALSA SRCR domains is applicable to all SRCR domains. We thus propose to have identified in SALSA a conserved functional mechanism for the SRCR class of proteins. (© 2020 Reichhardt et al.)
Databáze:	MEDLINE
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