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Solvation energetics and conformational change in EF‐hand proteins
Author(s) -
Ababou Abdessamad,
Desjarlais John R.
Publication year - 2001
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.33601
Subject(s) - conformational change , chemistry , calmodulin , solvation , circular dichroism , energetics , ef hand , calcium binding protein , crystallography , side chain , biophysics , nuclear magnetic resonance spectroscopy , stereochemistry , protein structure , calcium , biochemistry , biology , enzyme , ecology , organic chemistry , solvent , polymer
Calmodulin and other members of the EF‐hand protein family are known to undergo major changes in conformation upon binding Ca 2+ . However, some EF‐hand proteins, such as calbindin D9k, bind Ca 2+ without a significant change in conformation. Here, we show the importance of a precise balance of solvation energetics to conformational change, using mutational analysis of partially buried polar groups in the N‐terminal domain of calmodulin (N‐cam). Several variants were characterized using fluorescence, circular dichroism, and NMR spectroscopy. Strikingly, the replacement of polar side chains glutamine and lysine at positions 41 and 75 with nonpolar side chains leads to dramatic enhancement of the stability of the Ca 2+ ‐free state, a corresponding decrease in Ca 2+ ‐binding affinity, and an apparent loss of ability to change conformation to the open form. The results suggest a paradigm for conformational change in which energetic strain is accumulated in one state in order to modulate the energetics of change to the alternative state.