2K3S

HADDOCK-derived structure of the CH-domain of the smoothelin-like 1 complexed with the C-domain of apocalmodulin

Summary for 2K3S

• Entry DOI: 10.2210/pdb2k3s/pdb
• Related: 1F71 2JV9
• Descriptor: Smoothelin-like protein 1, Calmodulin (2 entities in total)
• Functional Keywords: apocalmodulin complex, calponin homology domain, smoothelin-like 1, haddock model, ch-domain, coiled coil, acetylation, calcium, methylation, protein binding
• Biological source: Mus musculus (mouse); More
• Cellular location: Cytoplasm, myofibril, sarcomere, I band: Q99LM3
• Total number of polymer chains: 2
• Total formula weight: 21431.26

Authors

Ishida, H.,Borman, M.A.,Ostrander, J.,Vogel, H.J.,MacDonald, J.A. (deposition date: 2008-05-15, release date: 2008-05-27, Last modification date: 2024-05-29)

Primary citation

Ishida, H.,Borman, M.A.,Ostrander, J.,Vogel, H.J.,MacDonald, J.A.
Solution structure of the calponin homology (CH) domain from the smoothelin-like 1 protein: a unique apocalmodulin-binding mode and the possible role of the C-terminal type-2 CH-domain in smooth muscle relaxation.
J.Biol.Chem., 283:20569-20578, 2008

PubMed Abstract: The SMTNL1 protein contains a single type-2 calponin homology (CH) domain at its C terminus that shares sequence identity with the smoothelin family of smooth muscle-specific proteins. In contrast to the smoothelins, SMTNL1 does not associate with F-actin in vitro, and its specific role in smooth muscle remains unclear. In addition, the biological function of the C-terminal CH-domains found in the smoothelin proteins is also poorly understood. In this work, we have therefore determined the solution structure of the CH-domain of mouse SMTNL1 (SMTNL1-CH; residues 346-459). The secondary structure and the overall fold for the C-terminal type-2 CH-domain is very similar to that of other CH-domains. However, two clusters of basic residues form a unique surface structure that is characteristic of SMTNL1-CH. Moreover, the protein has an extended C-terminal alpha-helix, which contains a calmodulin (CaM)-binding IQ-motif, that is also a distinct feature of the smoothelins. We have characterized the binding of apo-CaM to SMTNL1-CH through its IQ-motif by isothermal titration calorimetry and NMR chemical shift perturbation studies. In addition, we have used the HADDOCK protein-protein docking approach to construct a model for the complex of apo-CaM and SMTNL1-CH. The model revealed a close interaction of SMTNL1-CH with the two Ca(2+) binding loop regions of the C-terminal domain of apo-CaM; this mode of apo-CaM binding is distinct from previously reported interactions of apo-CaM with IQ-motifs. Finally, we comment on the putative role of the CH-domain in the biological function of SMTNL1.

PubMed: 18477568
DOI: 10.1074/jbc.M800627200

Experimental method

SOLUTION NMR