Metal-ion affinity and specificity in EF-hand proteins: Coordination geometry and domain plasticity in parvalbumin

M. Susan Cates, Michael B. Berry, Emai Lynn Ho, Qi Li, James D. Potter, George N. Phillips

Research output: Contribution to journalArticlepeer-review

68 Scopus citations


Background: The EF-hand family is a large set of Ca2+-binding proteins that contain characteristic helix-loop-helix binding motifs that are highly conserved in sequence. Members of this family include parvalbumin and many prominent regulatory proteins such as calmodulin and troponin C. EF-hand proteins are involved in a variety of physiological processes including cell- cycle regulation, second messenger production, muscle contraction, microtubule organization and vision. Results: We have determined the structures of parvalbumin mutants designed to explore the role of the last coordinating residue of the Ca2+-binding loop. An E101D substitution has been made in the parvalbumin EF site. The substitution decreases the Ca2+- binding affinity 100-fold and increases the Mg2+-binding affinity 10-fold. Both the Ca2+- and Mg2+-bound structures have been determined, and a structural basis has been proposed for the metal-ion-binding properties. Conclusions: The E101D mutation does not affect the Mg2+ coordination geometry of the binding loop, but it does pull the F helix 1.1 Å towards the loop. The E101 D-Ca2+ structure reveals that this mutant cannot obtain the sevenfold coordination preferred by Ca2+, presumably because of strain limits imposed by tertiary structure. Analysis of these results relative to previously reported structural information supports a model wherein the characteristics of the last coordinating residue and the plasticity of the Ca2+-binding loop delimit the allowable geometries for the coordinating sphere.

Original languageEnglish (US)
Pages (from-to)1269-1278
Number of pages10
Issue number10
StatePublished - Oct 15 1999
Externally publishedYes


  • Ca binding
  • EF-hand proteins
  • Mg binding
  • Parvalbumin
  • Protein plasticity

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology


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