 IQ Domain | |
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Structure:
 The IQ domain forms an uninterrupted seven-turn α-helix that is distinctly amphiphilic. The non-polar face of the helix switches sides after the fifth turn, providing an additional surface where contacts with ligand can occur. Residues important for interactions with calmodulin include a hydrophobic amino acid at position 1, a highly conserved glutamine at position 2, basic charges at positions 6 and 11, and a variable glycine at position 7. The substitution of this glycine with residues possessing bulky side chains, which occurs in approximately 50% of IQ domains, may provide some specificity for calmodulin interactions, as might the identity of the 6 intervening amino acids in the IQ consensus sequence.
Structure Reference:
Terrak, M. et al. (2002) Acta Crystallogr D Biol Crystallogr. 58(Pt10 Pt 2): 1882-5. PDB: 1N2D.
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Domain binding and function:
The IQ domain is approximately 25 amino acids in length and is widely distributed in nature. The motif conforms to the consensus sequence [I,L,V]QxxxRGxxx[R,K], which forms an amphiphilic seven-turn α-helix capable of binding calmodulin in a Ca2+-independent manner. IQ motifs result in different light chain conformations: compact and extended. Calmodulin mediates the effects of the major cellular second signal Ca2+, and can stimulate changes in the actin cytoskeleton through proteins such as myosin. Nearly all myosins possess between one and seven IQ domains, with most being found in multiple tandem repeats separated by 9-16 residues. Binding of calmodulin by IQ motifs from a diverse set of proteins might allow Ca2+ signaling to effect a wide range of cellular activities. Proteins found to contain at least one IQ domain include myosins, voltage-operated channels, several neuronal growth proteins, phosphatases, sperm surface proteins, Ras exchange proteins, spindle-associated proteins, a RasGAP-like protein and several plant-specific proteins.
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Examples of Proteins:
| IQ domain proteins |
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Binding partners |
| Myo2p (class V myosin) |  |
Mlc1p (calmodulin-like myosin light chain), Ca2+-independent |
| Neurogranin | |
CaM (calmodulin), Ca2+-independent and regulated by PKC phosphorylation of the IQ motif |
| Ras-GRF (exchange factor) | |
CaM (calmodulin), Ca2+-induced binding to IQ domain |
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Referenced in part on Cell Signaling Technology Website, Reference Section on Protein Domains. We gratefully acknowledge the following contributors:
Piers Nash1, Dan Lin3, Kathleen Binns2, Clark Wells2, Rob Ingham2, Terry Kubiseski2, Bernard Liu1, Matt Smith2,3, Ivan Blasutig2,3, Maria Sierra1, Caesar Lim2,3, Michael Arc1, Jim Fawcett2 and Tony Pawson2,3.
1. Ben May Institute for Cancer Research, The University of Chicago, Chicago, Illinois, 60637, USA
2. Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, M5G 1X5, Canada
3. Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, M5S 1A8, Canada
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