6BY2

Closed and deep-inactivated conformation of KcsA-T75A mutant

Summary for 6BY2

• Entry DOI: 10.2210/pdb6by2/pdb
• Descriptor: Antibody Heavy Chain, Antibody Light Chain, pH-gated potassium channel KcsA, ... (7 entities in total)
• Functional Keywords: kcsa, c-type inactivation, ion channel, potassium channel, membrane protein
• Biological source: Mus musculus; More
• Total number of polymer chains: 3
• Total formula weight: 58682.26

Authors

Labro, A.J.,Cortes, D.M.,Tilegenova, C.,Cuello, L.G. (deposition date: 2017-12-19, release date: 2018-05-09, Last modification date: 2024-11-06)

Primary citation

Labro, A.J.,Cortes, D.M.,Tilegenova, C.,Cuello, L.G.
Inverted allosteric coupling between activation and inactivation gates in K+channels.
Proc. Natl. Acad. Sci. U.S.A., 115:5426-5431, 2018

PubMed Abstract: The selectivity filter and the activation gate in potassium channels are functionally and structurally coupled. An allosteric coupling underlies C-type inactivation coupled to activation gating in this ion-channel family (i.e., opening of the activation gate triggers the collapse of the channel's selectivity filter). We have identified the second Threonine residue within the TTVGYGD signature sequence of K channels as a crucial residue for this allosteric communication. A Threonine to Alanine substitution at this position was studied in three representative members of the K-channel family. Interestingly, all of the mutant channels exhibited lack of C-type inactivation gating and an inversion of their allosteric coupling (i.e., closing of the activation gate collapses the channel's selectivity filter). A state-dependent crystallographic study of KcsA-T75A proves that, on activation, the selectivity filter transitions from a nonconductive and deep C-type inactivated conformation to a conductive one. Finally, we provide a crystallographic demonstration that closed-state inactivation can be achieved by the structural collapse of the channel's selectivity filter.

PubMed: 29735651
DOI: 10.1073/pnas.1800559115

Experimental method

X-RAY DIFFRACTION (2.35 Å)