Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Dec 28;293(52):20008-20009.
doi: 10.1074/jbc.H118.006869.

Structure of a transporter domain emerges

Affiliations

Structure of a transporter domain emerges

Chris Ulens. J Biol Chem. .

Abstract

Magnesium homeostasis relies on transporters like the CNNM family, but little information on these proteins' structure and regulation limits our understanding of their biology and functions in disease. New characterization of a conserved cytoplasmic domain now confirms the presence of a self-liganded architecture that is indispensable for Mg2+ efflux and suggests a possible role for a dimeric assembly.

PubMed Disclaimer

Conflict of interest statement

The author declares that he has no conflicts of interest with the contents of this article

Figures

Figure 1.
Figure 1.
Structural comparison of the HCN2 channel CNBD in complex with cAMP (PDB code 1q5o, left), the EAG1 channel CNBHD (PDB code 5k7l, middle), and the CNBHD of the CNNM3 transporter (right, this study). In the CNBHDs, the cyclic nucleotide–binding site is “self-liganded,” meaning part of the CNBHD sequence occupies the ligand binding site (Tyr-672 + Leu-674 in the case of EAG1 and Tyr-628 in the case of CNNM3). In the integral HCN and EAG channels, the CNBD quaternary assembly matches the tetramer assembly of the channel pore and C-linker domain (not shown in figure). In the CNNM3 transporter, the isolated CNBHD adopts a dimer assembly.

References

    1. Parry D. A., Mighell A. J., El-Sayed W., Shore R. C., Jalili I. K., Dollfus H., Bloch-Zupan A., Carlos R., Carr I. M., Downey L. M., Blain K. M., Mansfield D. C., Shahrabi M., Heidari M., Aref P., Abbasi M., Michaelides M., Moore A. T., Kirkham J., and Inglehearn C. F. (2009) Mutations in CNNM4 cause Jalili syndrome, consisting of autosomal-recessive cone-rod dystrophy and amelogenesis imperfecta. Am. J. Hum. Genet. 84, 266–273 10.1016/j.ajhg.2009.01.009 - DOI - PMC - PubMed
    1. Chen Y. S., Kozlov G., Fakih R., Funato Y., Miki H., and Gehring K. (2018) The cyclic nucleotide–binding homology domain of the integral membrane protein CNNM mediates dimerization and is required for Mg2+ efflux activity. (2018) J. Biol. Chem. 293, 19998–20007 10.1074/jbc.RA118.005672 - DOI - PMC - PubMed
    1. McKay D. B., and Steitz T. A. (1981) Structure of catabolite gene activator protein at 2.9 Å resolution suggests binding to left-handed B-DNA. Nature 290, 744–749 10.1038/290744a0 - DOI - PubMed
    1. Knighton D. R., Zheng J. H., Ten Eyck L. F., Ashford V. A., Xuong N. H., Taylor S. S., and Sowadski J. M. (1991) Crystal structure of the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase. Science 253, 407–414 10.1126/science.1862342 - DOI - PubMed
    1. Rehmann H., Das J., Knipscheer P., Wittinghofer A., and Bos J. L. (2006) Structure of the cyclic-AMP-responsive exchange factor Epac2 in its auto-inhibited state. Nature 439, 625–628 10.1038/nature04468 - DOI - PubMed

Publication types

LinkOut - more resources