RGD Reference Report - Functional coupling between the Kv1.1 channel and aldoketoreductase Kvbeta1. - Rat Genome Database

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Functional coupling between the Kv1.1 channel and aldoketoreductase Kvbeta1.

Authors: Pan, Y  Weng, J  Cao, Y  Bhosle, RC  Zhou, M 
Citation: Pan Y, etal., J Biol Chem. 2008 Mar 28;283(13):8634-42. doi: 10.1074/jbc.M709304200. Epub 2008 Jan 25.
RGD ID: 10047381
Pubmed: PMID:18222921   (View Abstract at PubMed)
PMCID: PMC2417172   (View Article at PubMed Central)
DOI: DOI:10.1074/jbc.M709304200   (Journal Full-text)

The Shaker family voltage-dependent potassium channels (Kv1) assemble with cytosolic beta-subunits (Kvbeta) to form a stable complex. All Kvbeta subunits have a conserved core domain, which in one of them (Kvbeta2) is an aldoketoreductase that utilizes NADPH as a cofactor. In addition to this core, Kvbeta1 has an N terminus that closes the channel by the N-type inactivation mechanism. Point mutations in the putative catalytic site of Kvbeta1 alter the on-rate of inactivation. Whether the core of Kvbeta1 functions as an enzyme and whether its enzymatic activity affects N-type inactivation had not been explored. Here, we show that Kvbeta1 is a functional aldoketoreductase and that oxidation of the Kvbeta1-bound cofactor, either enzymatically by a substrate or non-enzymatically by hydrogen peroxide or NADP(+), induces a large increase in open channel current. The modulation is not affected by deletion of the distal C terminus of the channel, which has been suggested in structural studies to interact with Kvbeta. The rate of increase in current, which reflects NADPH oxidation, is approximately 2-fold faster at 0-mV membrane potential than at -100 mV. Thus, cofactor oxidation by Kvbeta1 is regulated by membrane potential, presumably via voltage-dependent structural changes in Kv1.1 channels.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Kcnab1Ratregulation of delayed rectifier potassium channel activity involved_inIDA PMID:18222921UniProt 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Kcnab1Rataldo-keto reductase (NADPH) activity enablesIDA PMID:18222921UniProt 
Kcnab1Ratpotassium channel regulator activity enablesIDA PMID:18222921UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Kcnab1  (potassium voltage-gated channel subfamily A regulatory beta subunit 1)


Additional Information