PDBsum entry 5hxr

Membrane protein

PDB id: 5hxr

Contents

Protein chain

293 a.a.

Ligands

_CA ×2

OLC ×2

MYS ×9

PGE

Waters ×16

PDB id:

5hxr

Name:

Membrane protein

Title:

Structural mechanisms of extracellular ion exchange and induced binding-site occlusion in the sodium-calcium exchanger ncx_mj soaked with 2.5 mm na+ and 10mm ca2+

Structure:

Sodium,calcium exchanger. Chain: a. Fragment: unp residues 1-300. Engineered: yes. Mutation: yes

Source:

Methanocaldococcus jannaschii (strain atcc 43067 / dsm 2661 / jal-1 / jcm 10045 / nbrc 100440). Organism_taxid: 243232. Strain: atcc 43067 / dsm 2661 / jal-1 / jcm 10045 / nbrc 100440. Gene: mj0091. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.46Å R-factor: 0.224 R-free: 0.260

Authors:

J.Liao,Y.X.Jiang,J.D.Faraldo-Gomez

Key ref:

J.Liao et al. (2016). Mechanism of extracellular ion exchange and binding-site occlusion in a sodium/calcium exchanger. Nat Struct Biol, 23, 590-599. PubMed id: 27183196 DOI: 10.1038/nsmb.3230

Date:

31-Jan-16 Release date: 11-May-16

Protein chain

Q57556  (Y091_METJA) -  Uncharacterized membrane protein MJ0091 from Methanocaldococcus jannaschii (strain ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440)

Seq: 302 a.a.

Struc: 293 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1038/nsmb.3230

Nat Struct Biol 23:590-599 (2016)

PubMed id: 27183196

Mechanism of extracellular ion exchange and binding-site occlusion in a sodium/calcium exchanger.

J.Liao, F.Marinelli, C.Lee, Y.Huang, J.D.Faraldo-Gómez, Y.Jiang.

ABSTRACT

Na(+)/Ca(2+) exchangers use the Na(+) electrochemical gradient across the plasma membrane to extrude intracellular Ca(2+) and play a central role in Ca(2+) homeostasis. Here, we elucidate their mechanisms of extracellular ion recognition and exchange through a structural analysis of the exchanger from Methanococcus jannaschii (NCX_Mj) bound to Na(+), Ca(2+) or Sr(2+) in various occupancies and in an apo state. This analysis defines the binding mode and relative affinity of these ions, establishes the structural basis for the anticipated 3:1 Na(+)/Ca(2+)-exchange stoichiometry and reveals the conformational changes at the onset of the alternating-access transport mechanism. An independent analysis of the dynamics and conformational free-energy landscape of NCX_Mj in different ion-occupancy states, based on enhanced-sampling molecular dynamics simulations, demonstrates that the crystal structures reflect mechanistically relevant, interconverting conformations. These calculations also reveal the mechanism by which the outward-to-inward transition is controlled by the ion occupancy, thereby explaining the emergence of strictly coupled Na(+)/Ca(2+) antiport.