The 1.3-Å resolution structure of Nitrosomonas europaea Rh50 and mechanistic implications for NH3 transport by Rhesus family proteins
- Domenico Lupo*,
- Xiao-Dan Li*,
- Anne Durand†,
- Takashi Tomizaki‡,
- Baya Cherif-Zahar§,
- Giorgio Matassi¶,
- Mike Merrick†, and
- Fritz K. Winkler*,‖
- *Biomolecular Research, Paul Scherrer Institut, CH-5232 Villigen, Switzerland;
- †Department of Molecular Microbiology, John Innes Centre, Norwich NR4 7UH, United Kingdom;
- ‡Swiss Light Source, Paul Scherrer Institut, CH-5232 Villigen, Switzerland;
- §Université Paris Descartes, Institut National de la Santé et de la Recherche Médicale U845, Faculté de Medecine René Descartes, F-75015 Paris, France; and
- ¶Institut Jacques Monod Centre National de la Recherche Scientifique-Unite Mixte de Recherche 7592, Université Paris 6 et Université Paris 7, 2 Place Jussieu, 75251 Paris Cedex 05, France
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Edited by Stephen C. Harrison, Children's Hospital Boston, Boston, MA, and approved October 11, 2007 (received for review July 12, 2007)
Abstract
The Rhesus (Rh) proteins are a family of integral membrane proteins found throughout the animal kingdom that also occur in a number of lower eukaryotes. The significance of Rh proteins derives from their presence in the human red blood cell membrane, where they constitute the second most important group of antigens used in transfusion medicine after the ABO group. Rh proteins are related to the ammonium transport (Amt) protein family and there is considerable evidence that, like Amt proteins, they function as ammonia channels. We have now solved the structure of a rare bacterial homologue (from Nitrosomonas europaea) of human Rh50 proteins at a resolution of 1.3 Å. The protein is a trimer, and analysis of its subunit interface strongly argues that all Rh proteins are likely to be homotrimers and that the human erythrocyte proteins RhAG and RhCE/D are unlikely to form heterooligomers as previously proposed. When compared with structures of bacterial Amt proteins, NeRh50 shows several distinctive features of the substrate conduction pathway that support the concept that Rh proteins have much lower ammonium affinities than Amt proteins and might potentially function bidirectionally.
Footnotes
- ‖To whom correspondence should be addressed. E-mail: fritz.winkler{at}psi.ch
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Author contributions: D.L., X.-D.L., A.D., T.T., B.C.-Z., and G.M. performed research; D.L., X.-D.L., A.D., M.M., and F.K.W. analyzed data; and D.L., M.M., and F.K.W. wrote the paper.
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The authors declare no conflict of interest.
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This article is a PNAS Direct Submission.
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Data deposition: The atomic coordinates and structure factors have been deposited in the Protein Data Bank, www.pdb.org (PDB ID code 3B9W).
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This article contains supporting information online at www.pnas.org/cgi/content/full/0706563104/DC1.
- © 2007 by The National Academy of Sciences of the USA
