4MTF: Structural Basis Of Ca2+ Selectivity Of A Voltage-gated Calcium Channel

Citation:
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.
PDB ID: 4MTFDownload
MMDB ID: 115524
PDB Deposition Date: 2013/9/19
Updated in MMDB: 2013/12
Experimental Method:
x-ray diffraction
Resolution: 3.2  Å
Source Organism:
Similar Structures:
Biological Unit for 4MTF: tetrameric; determined by author and by software (PISA)
Molecular Components in 4MTF
Label Count Molecule
Proteins (4 molecules)
4
Ion Transport Protein
Molecule annotation
Chemicals (18 molecules)
1
2
2
16
* Click molecule labels to explore molecular sequence information.

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