4J9Z

Calcium-calmodulin complexed with the calmodulin binding domain from a small conductance potassium channel splice variant and NS309

Summary for 4J9Z

• Entry DOI: 10.2210/pdb4j9z/pdb
• Related: 1G4Y 3SJQ 4G27 4G28 4J9Y
• Descriptor: Small conductance calcium-activated potassium channel protein 2, Calmodulin, SULFATE ION, ... (7 entities in total)
• Functional Keywords: calcium binding, ef hand, sk2a channel fragment, transport protein-calcium binding complex, transport protein/calcium 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: 29883.48

Authors

Zhang, M.,Pascal, J.M.,Zhang, J.-F. (deposition date: 2013-02-17, release date: 2013-03-27, Last modification date: 2024-02-28)

Primary citation

Zhang, M.,Pascal, J.M.,Zhang, J.F.
Unstructured to structured transition of an intrinsically disordered protein peptide in coupling Ca2+-sensing and SK channel activation.
Proc.Natl.Acad.Sci.USA, 110:4828-4833, 2013

PubMed 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.

PubMed: 23487779
DOI: 10.1073/pnas.1220253110

Experimental method

X-RAY DIFFRACTION (1.66 Å)