PDBsum entry 4qnh

Ion transport/protein binding

PDB id: 4qnh

Contents

Protein chains

87 a.a.

146 a.a.

Ligands

SO4

Metals

_CA ×2

Waters ×187

PDB id:

4qnh

Name:

Ion transport/protein binding

Title:

Calcium-calmodulin (t79d) complexed with the calmodulin binding domain from a small conductance potassium channel sk2-a

Structure:

Small conductance calcium-activated potassium channel protein 2. Chain: b. Fragment: calmodulin binding domain (unp residues 396-487). Synonym: sk2, skca 2, skca2, kca2.2. Engineered: yes. Calmodulin. Chain: r. Synonym: cam.

Source:

Rattus norvegicus. Rat. Organism_taxid: 10116. Gene: kcnn2. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: calm1, calm, cam, cam1, calm2, cam2, camb, calm3, cam3, camc. Expression_system_taxid: 562

Resolution:

2.02Å R-factor: 0.184 R-free: 0.234

Authors:

M.Zhang,J.M.Pascal,D.E.Logothetis,J.F.Zhang

Key ref:

M.Zhang et al. (2014). Selective phosphorylation modulates the PIP2 sensitivity of the CaM-SK channel complex. Nat Chem Biol, 10, 753-759. PubMed id: 25108821 DOI: 10.1038/nchembio.1592

Date:

17-Jun-14 Release date: 06-Aug-14

Protein chain

P70604  (KCNN2_RAT) -  Small conductance calcium-activated potassium channel protein 2 from Rattus norvegicus

Seq: 580 a.a.

Struc: 87 a.a.*

Protein chain

No UniProt id for this chain

Struc: 146 a.a.

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chain B: E.C.?

DOI no: 10.1038/nchembio.1592

Nat Chem Biol 10:753-759 (2014)

PubMed id: 25108821

Selective phosphorylation modulates the PIP2 sensitivity of the CaM-SK channel complex.

M.Zhang, X.Y.Meng, M.Cui, J.M.Pascal, D.E.Logothetis, J.F.Zhang.

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.