6yb1
Crystal structure of an antiparallel octameric transmembrane coiled coil K2-CCTM-VbIcCrystal structure of an antiparallel octameric transmembrane coiled coil K2-CCTM-VbIc
Structural highlights
Publication Abstract from PubMedThe design of peptides that assemble in membranes to form functional ion channels is challenging. Specifically, hydrophobic interactions must be designed between the peptides and at the peptide-lipid interfaces simultaneously. Here, we take a multi-step approach towards this problem. First, we use rational de novo design to generate water-soluble alpha-helical barrels with polar interiors, and confirm their structures using high-resolution X-ray crystallography. These alpha-helical barrels have water-filled lumens like those of transmembrane channels. Next, we modify the sequences to facilitate their insertion into lipid bilayers. Single-channel electrical recordings and fluorescent imaging of the peptides in membranes show monodisperse, cation-selective channels of unitary conductance. Surprisingly, however, an X-ray structure solved from the lipidic cubic phase for one peptide reveals an alternative state with tightly packed helices and a constricted channel. To reconcile these observations, we perform computational analyses to compare the properties of possible different states of the peptide. Constructing ion channels from water-soluble alpha-helical barrels.,Scott AJ, Niitsu A, Kratochvil HT, Lang EJM, Sengel JT, Dawson WM, Mahendran KR, Mravic M, Thomson AR, Brady RL, Liu L, Mulholland AJ, Bayley H, DeGrado WF, Wallace MI, Woolfson DN Nat Chem. 2021 May 10. pii: 10.1038/s41557-021-00688-0. doi:, 10.1038/s41557-021-00688-0. PMID:33972753[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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