Diversity of conformational states and changes within the EF-hand protein superfamily

Proteins. 1999 Nov 15;37(3):499-507. doi: 10.1002/(sici)1097-0134(19991115)37:3<499::aid-prot17>3.0.co;2-y.


The EF-hand motif, which assumes a helix-loop-helix structure normally responsible for Ca2+ binding, is found in a large number of functionally diverse Ca2+ binding proteins collectively known as the EF-hand protein superfamily. In many superfamily members, Ca2+ binding induces a conformational change in the EF-hand motif, leading to the activation or inactivation of target proteins. In calmodulin and troponin C, this is described as a change from the closed conformational state in the absence of Ca2+ to the open conformational state in its presence. It is now clear from structures of other EF-hand proteins that this "closed-to-open" conformational transition is not the sole model for EF-hand protein structural response to Ca2+. More complex modes of conformational change are observed in EF-hand proteins that interact with a covalently attached acyl group (e.g., recoverin) and in those that dimerize (e.g., S100B, calpain). In fact, EF-hand proteins display a multitude of unique conformational states, together constituting a conformational continuum. Using a quantitative 3D approach termed vector geometry mapping (VGM), we discuss this tertiary structural diversity of EF-hand proteins and its correlation with target recognition.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Amino Acid Motifs
  • Calcium Signaling
  • Calcium-Binding Proteins / chemistry*
  • Calmodulin / chemistry
  • Helix-Loop-Helix Motifs
  • Molecular Conformation
  • Protein Conformation
  • Troponin C / chemistry


  • Calcium-Binding Proteins
  • Calmodulin
  • Troponin C