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Publication Abstract from PubMed

We describe a set of proteins in which a betagamma-crystallin domain pairs with an Ig-like domain, and which are confined to microbes, like bacteria, slime molds and fungi. DdCAD-1 (Ca(2+) -dependent cell adhesion molecule-1) and abundant perithecial protein (APP) represent this class of molecules. Using the crystal structure of APP-NTD (N-terminal domain of APP), we describe its mode of Ca(2+) binding and provide a generalized theme for correct identification of the Ca(2+) -binding site within this class of molecules. As a common feature, one of the two Ca(2+) -binding sites is non-functional in the betagamma-crystallin domains of these proteins. While APP-NTD binds Ca(2+) with a micromolar affinity which is comparable to DdCAD-1, APP surprisingly does not bind Ca(2+) . Crystal structures of APP and Ca(2+) -bound APP-NTD reveal that the interface interactions in APP render its Ca(2+) -binding site inoperative. Thus, heterodomain association provides a novel mode of Ca(2+) -binding regulation in APP. Breaking the interface interactions (mutating Asp30Ala, Leu132Ala and Ile135Ala) or separation from the Ig-like domain removes the constraints upon the required conformational transition and enables the betagamma-crystallin domain to bind Ca(2+) . In mechanistic detail, our work demonstrates an interdomain interface adapted to distinct functional niches in APP and its homolog DdCAD-1.

Interface interactions between betagamma-crystallin domain and Ig-like domain render Ca(2+) -binding site inoperative in abundant perithecial protein of Neurospora crassa.,Swaroop Srivastava S, Raman R, Kiran U, Garg R, Chadalawada S, Pawar AD, Sankaranarayanan R, Sharma Y Mol Microbiol. 2018 Dec;110(6):955-972. doi: 10.1111/mmi.14130. Epub 2018 Oct 16. PMID:30216631^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.