2HG5

Cs+ complex of a K channel with an amide to ester substitution in the selectivity filter

Summary for 2HG5

• Entry DOI: 10.2210/pdb2hg5/pdb
• Related: 2H8P 2HFE
• Descriptor: FAB HEAVY CHAIN, FAB LIGHT CHAIN, KCSA CHANNEL, ... (6 entities in total)
• Functional Keywords: channel, semi-synthetic, ester, membrane protein
• Biological source: Mus musculus (house mouse); More
• Cellular location: Cell membrane; Multi-pass membrane protein: 2HG5
• Total number of polymer chains: 3
• Total formula weight: 58463.56

Authors

Valiyaveetil, F.I.,MacKinnon, R.,Muir, T.W. (deposition date: 2006-06-26, release date: 2006-09-12, Last modification date: 2024-03-27)

Primary citation

Valiyaveetil, F.I.,Sekedat, M.,Mackinnon, R.,Muir, T.W.
Structural and Functional Consequences of an Amide-to-Ester Substitution in the Selectivity Filter of a Potassium Channel.
J.Am.Chem.Soc., 128:11591-11599, 2006

PubMed Abstract: The selectivity filter of K(+) channels comprises four contiguous ion binding sites, S1 through S4. Structural and functional data indicate that the filter contains on average two K(+) ions at any given time and that these ions reside primarily in two configurations, namely to sites S1 and S3 or to sites S2 and S4. Maximum ion flux through the channel is expected to occur when the energy difference between these two binding configurations is zero. In this study, we have used protein semisynthesis to selectively perturb site 1 within the filter of the KcsA channel through use of an amide-to-ester substitution. The modification alters K(+) conduction properties. The structure of the selectivity filter is largely unperturbed by the modification, despite the loss of an ordered water molecule normally located just behind the filter. Introduction of the ester moiety was found to alter the distribution of K(+), Rb(+,) and Cs(+) within the filter, with the most dramatic change found for Rb(+). The redistribution of ions is associated with the appearance of a partially hydrated ion just external to the filter, at a position where no ion is observed in the wild-type channel. The appearance of this new ion-binding site creates a change in the distance between a pair of K(+) ions some fraction of the time, apparently leading to a reduction in the ion conduction rate. Importantly, this finding suggests that the selectivity filter of a potassium channel is optimized both in terms of absolute ion occupancy and in terms of the separation in distance between the conducting ions.

PubMed: 16939283
DOI: 10.1021/ja0631955

Experimental method

X-RAY DIFFRACTION (2.75 Å)