7adi
KirBac3.1 W46R: role of a highly conserved tryptophan at the membrane-water interface of Kir channel
Structural highlights
FunctionIRK10_MAGMG Inward rectifier potassium channel that mediates potassium uptake into the cell. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. The inward rectification may be achieved by the blockage of outward current by cytoplasmic divalent metal ions and polyamines. Complements an E.coli mutant that is defective in K(+) uptake.[1] [2] [3] Publication Abstract from PubMedATP-sensitive potassium (K-ATP) channels are ubiquitously expressed on the plasma membrane of cells in several organs, including the heart, pancreas, and brain, and they govern a wide range of physiological processes. In pancreatic beta-cells, K-ATP channels composed of Kir6.2 and SUR1 play a key role in coupling blood glucose and insulin secretion. A tryptophan residue located at the cytosolic end of the transmembrane helix is highly conserved in eukaryote and prokaryote Kir channels. Any mutation on this amino acid causes a gain of function and neonatal diabetes mellitus. In this study, we have investigated the effect of mutation on this highly conserved residue on a KirBac channel (prokaryotic homolog of mammalian Kir6.2). We provide the crystal structure of the mutant KirBac3.1 W46R (equivalent to W68R in Kir6.2) and its conformational flexibility properties using HDX-MS. In addition, the detailed dynamical view of the mutant during the gating was investigated using the in silico method. Finally, functional assays have been performed. A comparison of important structural determinants for the gating mechanism between the wild type KirBac and the mutant W46R suggests interesting structural and dynamical clues and a mechanism of action of the mutation that leads to the gain of function. Integrative Study of the Structural and Dynamical Properties of a KirBac3.1 Mutant: Functional Implication of a Highly Conserved Tryptophan in the Transmembrane Domain.,Fagnen C, Bannwarth L, Oubella I, Zuniga D, Haouz A, Forest E, Scala R, Bendahhou S, De Zorzi R, Perahia D, Venien-Bryan C Int J Mol Sci. 2021 Dec 29;23(1). pii: ijms23010335. doi: 10.3390/ijms23010335. PMID:35008764[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||||
