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Related Experiment Videos

The DxDxDG motif for calcium binding: multiple structural contexts and implications for evolution.

Daniel J Rigden1, Michael Y Galperin

  • 1School of Biological Sciences, University of Liverpool, Crown St., Liverpool L69 7ZB, UK. drigden@liverpool.ac.uk <drigden@liverpool.ac.uk>

Journal of Molecular Biology
|October 13, 2004
PubMed
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The EF-hand is not the only structure for calcium-binding loops containing the DxDxDG motif. This motif appears in diverse protein structures, suggesting loop transplant and convergent evolution contribute to calcium-binding diversity.

Area of Science:

  • Biochemistry
  • Structural Biology
  • Evolutionary Biology

Background:

  • Calcium ions (Ca2+) are vital for numerous cellular functions and structural roles.
  • Calcium-binding proteins (CaBPs) often utilize the EF-hand motif, characterized by a helix-loop-helix structure with a DxDxDG sequence.
  • Recent discoveries include CaBPs with the DxDxDG motif but lacking canonical EF-hand helices.

Purpose of the Study:

  • To investigate the structural diversity of DxDxDG-containing CaBPs beyond the canonical EF-hand.
  • To analyze the evolutionary relationships and mechanisms shaping these calcium-binding loops.
  • To assess the implications for predicting calcium-binding capabilities from protein sequences.

Main Methods:

  • Utilized structural motif searches to analyze known DxDxDG-containing CaBPs.

Related Experiment Videos

  • Examined proteins where the DxDxDG motif's resemblance to EF-hands was not previously recognized.
  • Compared structural similarities and proposed evolutionary scenarios for motif distribution.

    • Main Results:

    • The EF-hand is one of many structural contexts for DxDxDG-like calcium-binding loops.
    • Homology is suggested for binuclear sites (anthrax protective antigen, human thrombospondin), but mononuclear sites show less clear evolutionary links.
    • Loop transplant and local convergent evolution are proposed as mechanisms for the diversity of DxDxDG motif structures.

    Conclusions:

    • The DxDxDG motif is versatile, appearing in various structural contexts beyond the EF-hand.
    • Evolutionary pathways for these motifs are complex, involving mechanisms like loop transplant.
    • Predicting calcium-binding solely from sequence is challenging due to structural and evolutionary diversity.