4MVO

Structural Basis for Ca2+ Selectivity of a Voltage-gated Calcium Channel

Summary for 4MVO

• Entry DOI: 10.2210/pdb4mvo/pdb
• Related: 4MS2 4MTF 4MTG 4MTO 4MVM
• Descriptor: Ion transport protein, 1,2-DIMYRISTOYL-SN-GLYCERO-3-PHOSPHOCHOLINE, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: tetrameric, voltage-gated ion channel, voltage-gated calcium channel, calcium selective, transport protein, membrane, metal transport
• Biological source: Arcobacter butzleri
• Total number of polymer chains: 4
• Total formula weight: 120813.63

Authors

Tang, L.,Gamal El-Din, T.M.,Payandeh, J.,Martinez, G.Q.,Heard, T.M.,Scheuer, T.,Zheng, N.,Catterall, W.A. (deposition date: 2013-09-24, release date: 2013-11-27, Last modification date: 2024-02-28)

Primary citation

Tang, L.,Gamal El-Din, T.M.,Payandeh, J.,Martinez, G.Q.,Heard, T.M.,Scheuer, T.,Zheng, N.,Catterall, W.A.
Structural basis for Ca2+ selectivity of a voltage-gated calcium channel.
Nature, 505:56-61, 2014

PubMed Abstract: Voltage-gated calcium (CaV) channels catalyse rapid, highly selective influx of Ca(2+) into cells despite a 70-fold higher extracellular concentration of Na(+). How CaV channels solve this fundamental biophysical problem remains unclear. Here we report physiological and crystallographic analyses of a calcium selectivity filter constructed in the homotetrameric bacterial NaV channel NaVAb. Our results reveal interactions of hydrated Ca(2+) with two high-affinity Ca(2+)-binding sites followed by a third lower-affinity site that would coordinate Ca(2+) as it moves inward. At the selectivity filter entry, Site 1 is formed by four carboxyl side chains, which have a critical role in determining Ca(2+) selectivity. Four carboxyls plus four backbone carbonyls form Site 2, which is targeted by the blocking cations Cd(2+) and Mn(2+), with single occupancy. The lower-affinity Site 3 is formed by four backbone carbonyls alone, which mediate exit into the central cavity. This pore architecture suggests a conduction pathway involving transitions between two main states with one or two hydrated Ca(2+) ions bound in the selectivity filter and supports a 'knock-off' mechanism of ion permeation through a stepwise-binding process. The multi-ion selectivity filter of our CaVAb model establishes a structural framework for understanding the mechanisms of ion selectivity and conductance by vertebrate CaV channels.

PubMed: 24270805
DOI: 10.1038/nature12775

Experimental method

X-RAY DIFFRACTION (3.296 Å)