6N7E

Crystal structure of the cytosolic domain of human CNNM2 in complex with AMP-PNP and Mg2+

Summary for 6N7E

• Entry DOI: 10.2210/pdb6n7e/pdb
• Related: 6MN6
• Descriptor: Metal transporter CNNM2,Metal transporter CNNM2, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: cnnm2, mg2+ transporter, cystathionine-beta-synthase domain, cyclic nucleotide-binding homology domain, atp-bound, closed conformation, membrane protein, metal transport
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 165429.76

Authors

Chen, Y.S.,Gehring, K. (deposition date: 2018-11-27, release date: 2019-12-04, Last modification date: 2023-10-11)

Primary citation

Chen, Y.S.,Kozlov, G.,Fakih, R.,Yang, M.,Zhang, Z.,Kovrigin, E.L.,Gehring, K.
Mg2+-ATP Sensing in CNNM, a Putative Magnesium Transporter.
Structure, 28:324-335.e4, 2020

PubMed Abstract: The family of cystathionine-β-synthase (CBS)-pair domain divalent metal cation transport mediators (CNNMs) is composed of four integral membrane proteins associated with Mg transport. Structurally, CNNMs contain large cytosolic regions composed of a CBS-pair and a cyclic nucleotide-binding homology (CNBH) domain. How these regulate Mg transport activity is unknown. Here, we determined the crystal structures of cytosolic fragments in two conformations: Mg-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-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-ATP binding and protein dimerization. Mutations that blocked either function prevented cellular Mg efflux activity. The results suggest Mg efflux is regulated by conformational changes associated with Mg-ATP binding to CNNM CBS-pair domains.

PubMed: 31864811
DOI: 10.1016/j.str.2019.11.016

Experimental method

X-RAY DIFFRACTION (3.5 Å)