Crystal structure of apo-calmodulin bound to the first two IQ motifs of myosin V reveals essential recognition features

Binding of trifluoperazine to apocalmodulin revealed by a combination of small-angle X-ray scattering and nuclear magnetic resonance

“…The analysis indicated that the main interaction and conformational changes occurred in the C-terminal domain and H may be involved in the binding process. Furthermore, the crystal structure of an apoCaM/myosin V IQ motifs complex revealed that the C-terminal domain interacts with the two IQ motifs (Houdusse et al, 2006). These three observations and the present result strongly suggest that the C-terminal domain plays a crucial role in interactions between apoCaM and TFP/target proteins.…”

“…In addition, the IQ motif from neuromodulin, IQASFR-GHITRKKLKGEK, does not bring about a change in the R g value (data not shown), indicating that the protein keeps a dumbbell shape. The dumbbell structure has been observed in the crystal structure of apoCaM complexed with the first two IQ motifs of myosin V (Houdusse et al, 2006). These two patterns in the molecular recognition infer that the flexible linker connecting the N-and C-terminal globular domains is influenced by the binding of TFP/target peptides to the C-terminal domain (Izumi et al, 2001).…”

“…There is increasing evidence that the C-terminal domain of apoCaM interacts with various peptides from target proteins (Cui et al, 2003;Yuan et al, 1999;Schumacher et al, 2004;Mori et al, 2003;Tsvetkov et al, 1999;Hill et al, 2000;Izumi et al, 2001;Houdusse et al, 2006). The crystal structure of the apoCaM/SK channel gating domain complex revealed that the Tyr435 side chain in the CaMbinding domain makes van der Waals contact with residues in E and H (Schumacher et al, 2004).…”

“…This was confirmed by crystallographic and nuclear magnetic resonance (NMR) studies on various target Ca 2+ CaM-binding proteins including MLCK, CaMdependent protein kinase (CaMK) and myristoylated alanine-rich Ckinase substrate (MARCKS) (reviewed in Ikura et al, 2002;Yamniuk & Vogel, 2004;Ikura & Ames, 2006). In contrast, although the interactions of apoCaM have been studied with some target proteins such as neurogranin, cyclic nucleotide phosphodiesterase (PDE), small conductance Ca 2+ -activated K + channel (SK channel), voltagegated sodium channel, MLCK and myosin V (Cui et al, 2003;Yuan et al, 1999;Mori et al, 2003;Tsvetkov et al, 1999;Hill et al, 2000;Bayley et al, 2003;Akyol et al, 2004;Tang et al, 2003;Jin et al, 2005;Houdusse et al, 2006), structural studies are very rare (Izumi et al, 2001;Schumacher et al, 2004).…”

Calmodulin has the Potential to Function as a Ca2+-Dependent Adaptor Protein

“…1H) has also revealed yet another variation on the wrap-around binding mode, where the apo-C-lobe of CaM adopts a semi-open conformation and forms numerous interactions with the target sequence, while the apo-N-lobe adopts a closed conformation and forms weaker interactions with the IQ domain. 21 Using several biophysical techniques we recently characterized the interaction between CaM isoforms (mammalian CaM, soybean CaM isoforms SCaM-1 and SCaM-4) and a novel CaMBD derived from the Nicotiana tabacum mitogen-activated protein kinase phosphatase (NtMKP1). 22 The NtMKP1 protein was initially identified as a CaM-binding protein by Ohashi and coworkers, 23 and the same group recently showed that CaM-binding NtMKP1 homologs are also present in other plant species as well.…”