The Top Loops of the C2 Domains from Synaptotagmin and Phospholipase A2 Control Functional Specificity

Stefan H. Gerber, Jose Rizo-Rey, Thomas C. Südhof

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

The phospholipid-binding specificities of C2 domains, widely distributed Ca2+-binding modules, differ greatly despite similar three-dimensional structures. To understand the molecular basis for this specificity, we have examined the synaptotagmin 1 C2A domain, which interacts in a primarily electrostatic, Ca2+-dependent reaction with negatively charged phospholipids, and the cytosolic phospholipase A2 (cPLA2) C2 domain, which interacts by a primarily hydrophobic Ca2+-dependent mechanism with neutral phospholipids. We show that grafting the short Ca2+-binding loops from the tip of the cPLA2 C2 domain onto the top of the synaptotagmin 1 I C2A domain confers onto the synaptotagmin 1 C2A domain the phospholipid binding specificity of the cPLA2 C2 domain, indicating that the functional specificity of C2 domains is determined by their short top loops.

Original languageEnglish (US)
Pages (from-to)32288-32292
Number of pages5
JournalJournal of Biological Chemistry
Volume276
Issue number34
DOIs
StatePublished - Aug 24 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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