7ADI

KirBac3.1 W46R: role of a highly conserved tryptophan at the membrane-water interface of Kir channel

Summary for 7ADI

• Entry DOI: 10.2210/pdb7adi/pdb
• Descriptor: Inward rectifier potassium channel Kirbac3.1, POTASSIUM ION, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: metal transport, ion channel, inward rectifier, membrane protein, potassium channel
• Biological source: Magnetospirillum magnetotacticum
• Total number of polymer chains: 2
• Total formula weight: 67649.10

Authors

Venien-Bryan, C.,Fagnen, C.,De Zorzi, R.,Bannwarth, L.,Oubella, I.,Haouz, A. (deposition date: 2020-09-15, release date: 2022-01-12, Last modification date: 2024-01-31)

Primary citation

Fagnen, C.,Bannwarth, L.,Oubella, I.,Zuniga, D.,Haouz, A.,Forest, E.,Scala, R.,Bendahhou, S.,De Zorzi, R.,Perahia, D.,Venien-Bryan, C.
Integrative Study of the Structural and Dynamical Properties of a KirBac3.1 Mutant: Functional Implication of a Highly Conserved Tryptophan in the Transmembrane Domain.
Int J Mol Sci, 23:-, 2021

PubMed Abstract: ATP-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 β-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.

PubMed: 35008764
DOI: 10.3390/ijms23010335

Experimental method

X-RAY DIFFRACTION (2.8 Å)