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

DOI: 10.26508/lsa.201900502 DOI Help

Authors: Martin P. Reichhardt (University of Oxford) , Vuokko Loimaranta (University of Turku) , Susan M. Lea (University of Oxford) , Steven Johnson (University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Life Science Alliance , VOL 3

State: Published (Approved)
Published: February 2020
Diamond Proposal Number(s): 18069

Open Access Open Access

Abstract: 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.

Subject Areas: Biology and Bio-materials

Instruments: I03-Macromolecular Crystallography , I04-Macromolecular Crystallography