Molecular mechanisms underlying KVS-1-MPS-1 complex assembly.
Formation of heteromeric complexes between voltage-gated K(+) (Kv) channels and accessory (beta) subunits is a widespread means to generate heterogeneity of K(+) current in the nervous system. Here we investigate the principles that determine the interactions of Caenorhabditis elegans MPS-1, a bifunctional beta-subunit that possesses kinase activity, with Kv channels. MPS-1 belongs to the evolutionarily conserved family of KCNE beta-subunits that modulate the functional properties of a variety of Kv channels and that, when defective, can cause congenital and acquired disease in Homo sapiens. In Chinese hamster ovary cells, MPS-1 forms stable complexes with different alpha-subunits. The transmembrane domain of MPS-1 is necessary and sufficient for MPS-1 complex formation. The hydropathicity of the transmembrane domain is an important factor controlling MPS-1 assembly. A highly hydrophobic MPS-1 mutant fails to interact with its endogenous channel partners when transgenically expressed in living worms. The hydropathic mechanism does not require specific points of contact between interacting proteins. This may allow MPS-1 to assemble with various Kv channels, presumably modifying the electrical properties of each.
Wang
Yi
Y
University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Department of Physiology and Biophysics, Piscataway, New Jersey 08854, USA.
Sesti
Federico
F
D000818:Animals; D030801:Animals, Genetically Modified; D016466:CHO Cells; D017173:Caenorhabditis elegans / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D015221:Potassium Channels / Q000737:chemistry* / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000235:genetics / Q000502:physiology; D055672:Static Electricity
D029742:Caenorhabditis elegans Proteins; C522188:KVS-1 protein, C elegans; C473893:MPS-1 protein, C elegans; D008565:Membrane Proteins; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated