Bovine and mouse SLO3 K+ channels: evolutionary divergence points to an RCK1 region of critical function.
The slo3 gene encodes a K(+) channel found only in mammalian testis. This is in contrast to slo1, which is expressed in many tissues. Genes pertaining to male reproduction, especially those involved in sperm production, evolve morphologically and functionally much faster than their nonsexual counterparts. A comparison of SLO3 channel amino acid sequences from several species revealed a high degree of structural divergence relative to their SLO1 channel paralogues. To reveal any biophysical differences accompanying this rapid structural divergence, we analyzed the functional properties of SLO3 channels from two species, bovine and mouse. We observed several functional differences including voltage range of activation, kinetics, and pH sensitivity. Although SLO3 channel proteins from these two species lack conservation in many structural regions, we found that the first two of these three functional differences map to the same loop structure in their RCK1 (regulator of K(+) conductance 1) domain, which links the intermediate RCK1 subdomain to the C-terminal subdomain. We found that small structural changes in this region produce major changes in the voltage range of activation and kinetics. This rapidly evolving loop peptide shows the greatest length and sequence polymorphisms within RCK1 domains from many different species. In SLO3 channels this region may permit evolutionary changes that tune the gating properties in different species.
Santi
Celia M
CM
Department of Anatomy and Neurobiology, Genetics, Washington University School of Medicine, St. Louis, Missouri 63110, USA. santic@pcg.wustl.edu
Butler
Alice
A
Kuhn
Julia
J
Wei
Aguan
A
Salkoff
Lawrence
L
D000595:Amino Acid Sequence; D000818:Animals; D001703:Biophysics / Q000379:methods; D002417:Cattle; D003001:Cloning, Molecular; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D007700:Kinetics; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D009865:Oocytes / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
C110627:Kcnu1 protein, mouse; D051036:Large-Conductance Calcium-Activated Potassium Channels; D015221:Potassium Channels; D011518:Proto-Oncogene Proteins; C490616:Ddx6 protein, mouse; D053487:DEAD-box RNA Helicases