Complex formation between calmodulin and a peptide from the intracellular loop of the gap junction protein connexin43: Molecular conformation and energetics of binding

Matti Myllykoski , Krzysztof Kuczera , Petri Kursula

Gap junctions are formed by a family of transmembrane proteins, connexins. Connexin43 is a widely studied member of the family, being ubiquitously expressed in a variety of tissues and a target of a large number of disease mutations. The intracellular loop of connexin43 has been shown to include a calmodulin binding domain, but detailed 3-dimensional data on the structure of the complex are not available. In this study, we used a synthetic peptide from this domain to reveal the conformation of the calmodulin-peptide complex by small angle X-ray scattering. Upon peptide binding, calmodulin lost its dumbbell shape, adopting a more globular conformation. We also studied the energetics of the interaction using calorimetry and computational methods. All our data indicate that calmodulin binds to the peptide from cx43 in the classical ‘collapsed' conformation.

Mots clés: calmodulin; gap junction; connexin43; solution structure; calorimetry; regulation

Matti Myllykoski, Krzysztof Kuczera, Petri Kursula. Complex formation between calmodulin and a peptide from the intracellular loop of the gap junction protein connexin43: Molecular conformation and energetics of binding. Biophysical Chemistry, 2009, 144 (3), pp.130. ⟨10.1016/j.bpc.2009.08.001⟩. ⟨hal-00573073⟩