4hpf | pdb_00004hpf
Structure of the human SLO3 gating ring
Structural highlights
FunctionKCNU1_HUMAN Testis-specific potassium channel activated by both intracellular pH and membrane voltage that mediates export of K(+). May represent the primary spermatozoan K(+) current. In contrast to KCNMA1/SLO1, it is not activated by Ca(2+) or Mg(2+). Critical for fertility. May play an important role in sperm osmoregulation required for the acquisition of normal morphology and motility when faced with osmotic challenges, such as those experienced after mixing with seminal fluid and entry into the vagina.[1] Publication Abstract from PubMedThe activation of eukaryotic SLO K(+) channels by intracellular cues, mediated by a cytoplasmic structure called the gating ring, is central to their physiological roles. SLO3 channels are exclusively expressed in mammalian sperm, where variations of intracellular pH are critical to cellular function. Previous studies primarily focused on the mouse SLO3 orthologue and revealed that, in murine sperm, SLO3 mediates a voltage- and alkalization-activated K(+) current essential to male fertility. Here we investigate the activation of the human SLO3 channel by intracellular pH at the functional and structural level. By using electrophysiology in a heterologous system, we show that human SLO3 opens upon intracellular pH increase and that its expression and functional properties are modulated by LRRC52, a testis-specific accessory subunit. We next present the crystal structure of the human SLO3 gating ring. Comparison with the known structures of the corresponding domain from SLO1, a Ca(2+)-activated homologue, suggests that the SLO3 gating ring structure may represent an open state. Together, these results present insights into the function of a protein expected to be critical for human reproduction and provide a framework to study the mechanism of pH gating in SLO3 channels. Functional and structural analysis of the human SLO3 pH- and voltage-gated K+ channel.,Leonetti MD, Yuan P, Hsiung Y, Mackinnon R Proc Natl Acad Sci U S A. 2012 Nov 20;109(47):19274-9. doi:, 10.1073/pnas.1215078109. Epub 2012 Nov 5. PMID:23129643[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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