IQ-motif selectivity in human IQGAP2 and IQGAP3: Binding of calmodulin and myosin essential light chain

Erwan Atcheson, Elaine Hamilton, Sewel Pathmanathan, Brett Greer, Pat Harriott, David J. Timson

Research output: Contribution to journalArticlepeer-review

Abstract

The IQGAP [IQ-motif-containing GAP (GTPase-activating protein)] family members are eukaryotic proteins that act at the interface between cellular signalling and the cytoskeleton. As such they collect numerous inputs from a variety of signalling pathways. A key binding partner is the calcium-sensing protein CaM (calmodulin). This protein binds mainly through a series of IQ-motifs which are located towards the middle of the primary sequence of the IQGAPs. In some IQGAPs, these motifs also provide binding sites for CaM-like proteins such as myosin essential light chain and S100B. Using synthetic peptides and native gel electrophoresis, the binding properties of the IQ-motifs from human IQGAP2 and IQGAP3 have been mapped. The second and third IQ-motifs in IQGAP2 and all four of the IQ-motifs of IQGAP3 interacted with CaM in the presence of calcium ions. However, there were differences in the type of interaction: while some IQ-motifs were able to form complexes with CaM which were stable under the conditions of the experiment, others formed more transient interactions. The first IQ-motifs from IQGAP2 and IQGAP3 formed transient interactions with CaM in the absence of calcium and the first motif from IQGAP3 formed a transient interaction with the myosin essential light chain Mlc1sa. None of these IQ-motifs interacted with S100B. Molecular modelling suggested that all of the IQ-motifs, except the first one from IQGAP2 formed α-helices in solution. These results extend our knowledge of the selectivity of IQ-motifs for CaM and related proteins.

Original languageEnglish
Pages (from-to)371-379
Number of pages9
JournalBioscience Reports
Volume31
Issue number5
DOIs
Publication statusPublished - 1 Oct 2011

Keywords

  • α-helical peptide
  • Calcium-dependent interaction
  • IQ-motif
  • IQ-motif-containing gtpase-activating protein (iqgap)
  • Myosin essential light chain
  • Native gel electrophoresis

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