Structural highlights
Function
KCMB2_HUMAN Regulatory subunit of the calcium activated potassium KCNMA1 (maxiK) channel. Modulates the calcium sensitivity and gating kinetics of KCNMA1, thereby contributing to KCNMA1 channel diversity. Acts as a negative regulator that confers rapid and complete inactivation of KCNMA1 channel complex. May participate in KCNMA1 inactivation in chromaffin cells of the adrenal gland or in hippocampal CA1 neurons.[1] [2]
Publication Abstract from PubMed
The auxiliary beta-subunit KCNMB2 (beta(2)) endows the non-inactivating large conductance Ca(2+)- and voltage-dependent potassium (BK) channel with fast inactivation. This process is mediated by the N terminus of KCNMB2 and closely resembles the "ball-and-chain"-type inactivation observed in voltage-gated potassium channels. Here we investigated the solution structure and function of the KCNMB2 N terminus (amino acids 1-45, BKbeta(2)N) using NMR spectroscopy and patch clamp recordings. BKbeta(2)N completely inactivated BK channels when applied to the cytoplasmic side; its interaction with the BK alpha-subunit is characterized by a particularly slow dissociation rate and an affinity in the upper nanomolar range. The BKbeta(2)N structure comprises two domains connected by a flexible linker: the pore-blocking "ball domain" (formed by residues 1-17) and the "chain domain" (between residues 20-45) linking it to the membrane segment of KCNMB2. The ball domain is made up of a flexible N terminus anchored at a well ordered loop-helix motif. The chain domain consists of a 4-turn helix with an unfolded linker at its C terminus. These structural properties explain the functional characteristics of BKbeta(2)N-mediated inactivation.
NMR structure of the "ball-and-chain" domain of KCNMB2, the beta 2-subunit of large conductance Ca2+- and voltage-activated potassium channels.,Bentrop D, Beyermann M, Wissmann R, Fakler B J Biol Chem. 2001 Nov 9;276(45):42116-21. Epub 2001 Aug 21. PMID:11517232[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Wallner M, Meera P, Toro L. Molecular basis of fast inactivation in voltage and Ca2+-activated K+ channels: a transmembrane beta-subunit homolog. Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):4137-42. PMID:10097176
- ↑ Xia XM, Ding JP, Lingle CJ. Molecular basis for the inactivation of Ca2+- and voltage-dependent BK channels in adrenal chromaffin cells and rat insulinoma tumor cells. J Neurosci. 1999 Jul 1;19(13):5255-64. PMID:10377337
- ↑ Bentrop D, Beyermann M, Wissmann R, Fakler B. NMR structure of the "ball-and-chain" domain of KCNMB2, the beta 2-subunit of large conductance Ca2+- and voltage-activated potassium channels. J Biol Chem. 2001 Nov 9;276(45):42116-21. Epub 2001 Aug 21. PMID:11517232 doi:10.1074/jbc.M107118200
