Crystal structures of apocalmodulin and an apocalmodulin/SK potassium channel gating domain complex.
Small conductance Ca2+-activated K+ channels (SK channels) are composed of the pore-forming alpha subunit and calmodulin (CaM). CaM binds to a region of the alpha subunit called the CaM binding domain (CaMBD), located intracellular and immediately C-terminal to the inner helix gate, in either the presence or absence of Ca2+. SK gating occurs when Ca2+ binds the N lobe of CaM thereby transmitting the signal to the attached inner helix gate to open. Here we present crystal structures of apoCaM and apoCaM/SK2 CaMBD complex. Several apoCaM crystal forms with multiple (12) packing environments reveal the same EF hand domain-swapped dimer providing potentially new insight into CaM regulation. The apoCaM/SK2 CaMBD structure, combined with our Ca2+/CaM/CaMBD structure suggests that Ca2+ binding induces folding and dimerization of the CaMBD, which causes large CaMBD-CaM C lobe conformational changes, including a >90 degrees rotation of the region of the CaMBD directly connected to the gate.
Schumacher
Maria A
MA
Department of Biochemistry and Molecular Biology, Oregon Health & Science University, Portland, OR 97239 USA. schumacm@ohsu.edu
Crum
Matthew
M
Miller
Marshall C
MC
D001059:Apoproteins / Q000737:chemistry* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000737:chemistry* / Q000378:metabolism; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D019281:Dimerization; D024681:Potassium Channels, Calcium-Activated / Q000737:chemistry* / Q000378:metabolism; D017434:Protein Structure, Tertiary
D001059:Apoproteins; D002147:Calmodulin; D024681:Potassium Channels, Calcium-Activated; D002118:Calcium