Structure and Ca²⁺-binding properties of the tandem C₂ domains of E-Syt2

Structure. 2014 Feb 4;22(2):269-80. doi: 10.1016/j.str.2013.11.011. Epub 2013 Dec 26.


Contacts between the endoplasmic reticulum and the plasma membrane involve extended synaptotagmins (E-Syts) in mammals or tricalbins in yeast, proteins with multiple C₂ domains. One of the tandem C₂ domains of E-Syt2 is predicted to bind Ca²⁺, but no Ca²⁺-dependent function has been attributed to this protein. We have determined the crystal structures of the tandem C₂ domains of E-Syt2 in the absence and presence of Ca²⁺ and analyzed their Ca²⁺-binding properties by nuclear magnetic resonance spectroscopy. Our data reveal an unexpected V-shaped structure with a rigid orientation between the two C₂ domains that is not substantially altered by Ca²⁺. The E-Syt2 C2A domain binds up to four Ca²⁺ ions, whereas the C₂B domain does not bind Ca²⁺. These results suggest that E-Syt2 performs an as yet unidentified Ca²⁺-dependent function through its C₂A domain and uncover fundamental differences between the properties of the tandem C₂ domains of E-Syts and synaptotagmins.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Binding Sites
  • Calcium / chemistry*
  • Circular Dichroism
  • DNA, Complementary / metabolism
  • Endoplasmic Reticulum / metabolism
  • Escherichia coli / metabolism
  • Humans
  • Ions
  • Magnetic Resonance Spectroscopy
  • Mutation
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Signal Transduction
  • Synaptotagmins / chemistry*
  • Temperature
  • X-Ray Diffraction


  • DNA, Complementary
  • ESYT2 protein, human
  • Ions
  • Synaptotagmins
  • Calcium