Allostery in Orai1 binding to calmodulin revealed from conformational thermodynamics. Issue 2 (22nd January 2019)

• Record Type: Journal Article
• Authors: Maganti, Lakshmi; Dutta, Sutapa; Ghosh, Mahua; Chakrabarti, J.
• Is Part Of: Journal of biomolecular structure & dynamics. Volume 37:Issue 2(2019)
• Page Start: 493
• Page End: 502
• Publication Date: 2019-01-22
• Subjects: calmodulin-Orai1 complex -- molecular dynamics -- conformational thermodynamics -- allostery; Biomolecules -- Periodicals; Molecular structure -- Periodicals; Molecular Biology -- Periodicals; Biomechanics -- Periodicals; 572
• DOI: 10.1080/07391102.2018.1430617
• Languages: English
• ISSNs: 0739-1102

Abstract

Abstract : Here, we study microscopic mechanism of complex formation between Ca 2+ -bound calmodulin (holoCaM) and Orai1 that regulates Ca 2+ -dependent inactivation process in eukaryotic cells. We compute conformational thermodynamic changes in holoCaM with respect to complex of Orai1 bound to C-terminal domain of holoCaM using histograms of dihedral angles of the proteins over trajectories from molecular dynamics simulations. Our analysis shows that the N-terminal domain residues L4, T5, Q41, N42, T44 and E67 of holoCaM get destabilized and disordered due to Orai1 binding to C-terminal domain of calmodulin affect the N-terminal domain residues. Among these residues, polar T44, having maximum destabilization and disorder via backbone fluctuations, shows the largest change in solvent exposure. This suggests that N-terminal domain is allosterically regulated via T44 by the binding of Orai1 to the C-terminal domain.