PDBsum entry 4mvs

Metal transport

PDB id: 4mvs

Contents

Protein chains

219 a.a.

Ligands

PX4 ×16

Metals

_CD ×5

Waters ×6

PDB id:

4mvs

Name:

Metal transport

Title:

Structural basis for ca2+ selectivity of a voltage-gated calcium channel

Structure:

Ion transport protein. Chain: a, b, c, d. Engineered: yes

Source:

Arcobacter butzleri. Organism_taxid: 367737. Strain: rm4018. Gene: abu_1752. Expressed in: trichoplusia ni. Expression_system_taxid: 7111.

Resolution:

3.30Å R-factor: 0.235 R-free: 0.269

Authors:

L.Tang,T.M.Gamal El-Din,J.Payandeh,G.Q.Martinez,T.M.Heard,T.Scheuer, N.Zheng,W.A.Catterall

Key ref:

L.Tang et al. (2014). Structural basis for Ca2+ selectivity of a voltage-gated calcium channel. Nature, 505, 56-61. PubMed id: 24270805 DOI: 10.1038/nature12775

Date:

24-Sep-13 Release date: 27-Nov-13

Protein chains

A8EVM5  (A8EVM5_ARCB4) -  Ion transport protein from Aliarcobacter butzleri (strain RM4018)

Seq: 267 a.a.

Struc: 219 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1038/nature12775

Nature 505:56-61 (2014)

PubMed id: 24270805

Structural basis for Ca2+ selectivity of a voltage-gated calcium channel.

L.Tang, T.M.Gamal El-Din, J.Payandeh, G.Q.Martinez, T.M.Heard, T.Scheuer, N.Zheng, W.A.Catterall.

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.