4QNH

Calcium-calmodulin (T79D) complexed with the calmodulin binding domain from a small conductance potassium channel SK2-a

Summary for 4QNH

• Entry DOI: 10.2210/pdb4qnh/pdb
• Related: 4J9Y
• Descriptor: Small conductance calcium-activated potassium channel protein 2, Calmodulin, SULFATE ION, ... (5 entities in total)
• Functional Keywords: ion channel, ion transport-protein binding complex, ion transport/protein binding
• Biological source: Rattus norvegicus (rat); More
• Cellular location: Membrane; Multi-pass membrane protein: P70604; Cytoplasm, cytoskeleton, spindle: P62161
• Total number of polymer chains: 2
• Total formula weight: 29286.14

Authors

Zhang, M.,Pascal, J.M.,Logothetis, D.E.,Zhang, J.F. (deposition date: 2014-06-17, release date: 2014-08-06, Last modification date: 2024-02-28)

Primary citation

Zhang, M.,Meng, X.Y.,Cui, M.,Pascal, J.M.,Logothetis, D.E.,Zhang, J.F.
Selective phosphorylation modulates the PIP2 sensitivity of the CaM-SK channel complex.
Nat.Chem.Biol., 10:753-759, 2014

PubMed Abstract: Phosphatidylinositol bisphosphate (PIP2) regulates the activities of many membrane proteins, including ion channels, through direct interactions. However, the affinity of PIP2 is so high for some channel proteins that its physiological role as a modulator has been questioned. Here we show that PIP2 is a key cofactor for activation of small conductance Ca2+-activated potassium channels (SKs) by Ca(2+)-bound calmodulin (CaM). Removal of the endogenous PIP2 inhibits SKs. The PIP2-binding site resides at the interface of CaM and the SK C terminus. We further demonstrate that the affinity of PIP2 for its target proteins can be regulated by cellular signaling. Phosphorylation of CaM T79, located adjacent to the PIP2-binding site, by casein kinase 2 reduces the affinity of PIP2 for the CaM-SK channel complex by altering the dynamic interactions among amino acid residues surrounding the PIP2-binding site. This effect of CaM phosphorylation promotes greater channel inhibition by G protein-mediated hydrolysis of PIP2.

PubMed: 25108821
DOI: 10.1038/nchembio.1592

Experimental method

X-RAY DIFFRACTION (2.02 Å)