PDBsum entry 4j9y

Transport protein/calcium binding

PDB id: 4j9y

Contents

Protein chains

89 a.a.

146 a.a.

Ligands

SO4 ×3

GOL

Metals

_CA ×2

Waters ×321

PDB id:

4j9y

Name:

Transport protein/calcium binding

Title:

Calcium-calmodulin complexed with the calmodulin binding domain from a small conductance potassium channel splice variant

Structure:

Small conductance calcium-activated potassium channel protein 2. Chain: b. Fragment: calmodulin binding domain (unp residues 396-487). Synonym: sk2a, 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:

1.51Å R-factor: 0.184 R-free: 0.216

Authors:

M.Zhang,J.M.Pascal,J.-F.Zhang

Key ref:

M.Zhang et al. (2013). Unstructured to structured transition of an intrinsically disordered protein peptide in coupling Ca²⁺-sensing and SK channel activation. Proc Natl Acad Sci U S A, 110, 4828-4833. PubMed id: 23487779 DOI: 10.1073/pnas.1220253110

Date:

17-Feb-13 Release date: 27-Mar-13

Protein chain

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

Seq: 580 a.a.

Struc: 89 a.a.*

Protein chain

P0DP29  (CALM1_RAT) -  Calmodulin-1 from Rattus norvegicus

Seq: 149 a.a.

Struc: 146 a.a.

* PDB and UniProt seqs differ at 5 residue positions (black crosses)

DOI no: 10.1073/pnas.1220253110

Proc Natl Acad Sci U S A 110:4828-4833 (2013)

PubMed id: 23487779

Unstructured to structured transition of an intrinsically disordered protein peptide in coupling Ca²⁺-sensing and SK channel activation.

M.Zhang, J.M.Pascal, J.F.Zhang.

ABSTRACT

Most proteins, such as ion channels, form well-organized 3D structures to carry out their specific functions. A typical voltage-gated potassium channel subunit has six transmembrane segments (S1-S6) to form the voltage-sensing domain and the pore domain. Conformational changes of these domains result in opening of the channel pore. Intrinsically disordered (ID) proteins/peptides are considered equally important for the protein functions. However, it is difficult to explore the structural features underlying the functions of ID proteins/peptides by conventional methods, such as X-ray crystallography, because of the flexibility of their secondary structures. Unlike voltage-gated potassium channels, families of small- and intermediate-conductance Ca(2+)-activated potassium (SK/IK) channels with important roles in regulating membrane excitability are activated exclusively by Ca(2+)-bound calmodulin (CaM). Upon binding of Ca(2+) to CaM, a 2 × 2 structure forms between CaM and the CaM-binding domain. A channel fragment that connects S6 and the CaM-binding domain is not visible in the protein crystal structure, suggesting that this fragment is an ID fragment. Here we show that the conformation of the ID fragment in SK channels becomes readily identifiable in the presence of NS309, the most potent compound that potentiates the channel activities. This well-defined conformation of the ID fragment, stabilized by NS309, increases the channel open probability at a given Ca(2+) concentration. Our results demonstrate that the ID fragment, itself a target for drugs modulating SK channel activities, plays a unique role in coupling Ca(2+) sensing by CaM and mechanical opening of SK channels.