Ababou, Abdessamad, Shenvi, Ryan A. and Desjarlais, John R. (2001) Long-Range Effects on Calcium Binding and Conformational Change in the N-Domain of Calmodulin†. Biochemistry, 40 (42). pp. 12719-12726. ISSN 0006-2960
Abstract

Proteins within the EF-hand protein family exhibit different conformational responses to Ca2+ binding. Calmodulin and other members of the EF-hand protein family undergo major changes in conformation upon binding Ca2+. However, some EF-hand proteins, such as calbindin D9k (Clb), bind Ca2+ without a significant change in conformation. Here, we investigate the effects of replacement of a leucine at position 39 of the N-terminal domain of calmodulin (N-Cam) with a phenylalanine derived from Clb. This variant is studied alone and in the context of other mutations that affect the conformational properties of N-Cam. Strikingly, the introduction of Phe39, which is distant from the calcium binding sites, leads to a significant enhancement of Ca2+ binding affinity, even in the context of other mutations which trap the protein in the closed form. The results yield novel insights into the evolution of EF-hand proteins as calcium sensors versus calcium buffers.

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