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Modulation of Weak Protein‐Protein Interaction by Molecular Crowding
Author(s) -
Srinivasan P.
Publication year - 2017
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201701904
Subject(s) - orai1 , biophysics , stim1 , microbiology and biotechnology , chemistry , protein folding , macromolecular crowding , biology , biochemistry , membrane , macromolecule
Many membrane‐targeted signaling proteins undergo self‐associated homo‐oligomerization for triggering a cascade of downstream events in cells. Unraveling thermodynamic properties influencing homo‐oligomerization of large proteins in cell environment would bring valuable insight into biological signaling. Using Stromal Interaction Molecule 1 (STIM1) and Calcium Release‐Activated Calcium Channel Protein (ORAI1) coupling machinery as a model system, here I present invitro biophysical and biochemical evidences to explicate activation mechanism of STIM1 and its stabilization from energetics standpoint. Analyses of molecular arrangements using entropy and free energy estimates indicate homo‐oligomerization by molecular crowding is energetically favorable to form ordered structures of STIM1 to interact with ORAI1. A corollary of this finding is activated human STIM1 ‘puncta’ observed in over‐expressed cell biology experiment perhaps represents a more ordered non‐equilibrium state at which leucines of the cytoplasmic STIM1 fragment are shielded from solvent by energetically efficient molecular crowding.