Structure-Inspired Functional Discovery for a Family of Novel Anion Channels

来源 :The 3rd Ion Channel Conference: Ion channels-Structure, Func | 被引量 : 0次 | 上传用户:CBHHOLY
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  Stomata pores, formed by two kidney shape guard cell in the plant leaves, are the major gateway for CO2 influx for photosynthesis and water loss through transpiration.SLACI in the guard cell controls stomata closure in response to environmental stimuli, including drought, elevated CO2 and Ozone.Our pan-genomics search found a total of ~800 SLAC1 related protein members (Now called SLAC superfamily), including 47 plant SLAC1 and close homologs (SLAHs), and a set of bacterial TehA proteins.By using structural genomics approaches, we determined the crystal structure of TehA from Haemophilus influenza (HiTehA) at 1.2 (A), representing one of the highest resolution membrane protein structures determined to date.The structure shows that TehA is a symmetric trimer and each protomer forms a pore.The pore is occluded by the side chain of an absolutely conserved phenylalanine (Phe262 in HiTehA, Phe450 in AtSLACI) across the SLAC superfamily.The TehA structure represents a novel fold, with 10 transmenbrane segments arranged in a quasi five-fold symmetry.We gained insights into the gating mechanism and selectivity of SLAC1 channel from functional studies inspired by the homologous TehA structure.Remarkably, the TehA structure revealed that the conserved phenylalanine residue (Phe262) adopts a high energy conformation.Together with consistent results from mutagenesis studies, this allowed us to propose a convincing mechanism for SLAC1 gating control by phosphorylation.Electrostatic features of the pore coupled with electrophysiological characteristics suggest that selectivity among different anions is largely a function of the energetic cost of ion dehydration.
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