Structure of a Human A-type Potassium Channel Interacting Protein DPPX, a Member of the Dipeptidyl Aminopeptidase Family

It has recently been reported that dipeptidyl aminopeptidase X (DPPX) interacts with the voltage-gated potassium channel Kv4 and that co-expression of DPPX together with Kv4 pore forming α-subunits, and potassium channel interacting proteins (KChIPs), reconstitutes properties of native A-type potass...

Full description

Saved in:
Bibliographic Details
Published in:Journal of molecular biology 2004-10, Vol.343 (4), p.1055-1065
Main Authors: Strop, Pavel, Bankovich, Alexander J., Hansen, Kirk C., Christopher Garcia, K., Brunger, Axel T.
Format: Article
Language:English
Subjects:
Alternative Splicing
Catalytic Domain
Cystine - chemistry
Cystine - genetics
Cystine - metabolism
dipeptidyl aminopeptidase
Dipeptidyl-Peptidases and Tripeptidyl-Peptidases - chemistry
Dipeptidyl-Peptidases and Tripeptidyl-Peptidases - metabolism
DPP6
DPPX
Glycosylation
Humans
Isoenzymes - chemistry
Isoenzymes - metabolism
Potassium Channels, Voltage-Gated - metabolism
Protein Structure, Quaternary
Protein Structure, Tertiary
serine protease
Shal Potassium Channels
Static Electricity
voltage gated potassium channel
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:It has recently been reported that dipeptidyl aminopeptidase X (DPPX) interacts with the voltage-gated potassium channel Kv4 and that co-expression of DPPX together with Kv4 pore forming α-subunits, and potassium channel interacting proteins (KChIPs), reconstitutes properties of native A-type potassium channels in vitro. Here we report the X-ray crystal structure of the extracellular domain of human DPPX determined at 3.0 Å resolution. This structure reveals the potential for a surface electrostatic change based on the protonation state of histidine. Subtle changes in extracellular pH might modulate the interaction of DPPX with Kv4.2 and possibly with other proteins. We propose models of DPPX interaction with the voltage-gated potassium channel complex. The dimeric structure of DPPX is highly homologous to the related protein DPP-IV. Comparison of the active sites of DPPX and DPP-IV reveals loss of the catalytic serine residue but the presence of an additional serine near the “active” site. However, the arrangement of residues is inconsistent with that of canonical serine proteases and DPPX is unlikely to function as a protease (dipeptidyl aminopeptidase).
ISSN:0022-2836
1089-8638
DOI:10.1016/j.jmb.2004.09.003