5Z6D

Interface interactions between beta gamma-crystallin domain and Ig-like domain render Ca2+-binding site inoperative in abundant perithecial protein of Neurospora crassa.

(2018) Mol Microbiol 110: 955-972

• PubMed: 30216631 Search on PubMed
• DOI: https://doi.org/10.1111/mmi.14130
• Primary Citation of Related Structures:  
  5Z6D, 5Z6E


• PubMed Abstract: 
  

  We describe a set of proteins in which a βγ-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 βγ-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 βγ-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.

   View More

---

Organizational Affiliation: 

CSIR - Centre for Cellular and Molecular Biology (CCMB), Hyderabad, 500 007, India.