6mn6

Publication Abstract from PubMed

The family of cystathionine-beta-synthase (CBS)-pair domain divalent metal cation transport mediators (CNNMs) is composed of four integral membrane proteins associated with Mg(2+) transport. Structurally, CNNMs contain large cytosolic regions composed of a CBS-pair and a cyclic nucleotide-binding homology (CNBH) domain. How these regulate Mg(2+) transport activity is unknown. Here, we determined the crystal structures of cytosolic fragments in two conformations: Mg(2+)-ATP-analog bound and ligand free. The structures reveal open and closed conformations with functionally important contacts not observed in structures of the individual domains. We also identified a second Mg(2+)-binding region in the CBS-pair domain and a different dimerization interface for the CNBH domain. Analytical ultracentrifugation and isothermal titration calorimetry experiments revealed a tight correlation between Mg(2+)-ATP binding and protein dimerization. Mutations that blocked either function prevented cellular Mg(2+) efflux activity. The results suggest Mg(2+) efflux is regulated by conformational changes associated with Mg(2+)-ATP binding to CNNM CBS-pair domains.

Mg(2+)-ATP Sensing in CNNM, a Putative Magnesium Transporter.,Chen YS, Kozlov G, Fakih R, Yang M, Zhang Z, Kovrigin EL, Gehring K Structure. 2019 Dec 10. pii: S0969-2126(19)30434-4. doi:, 10.1016/j.str.2019.11.016. PMID:31864811^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.