title: Molecular basis of transport and regulation in the Na(+)/betaine symporter BetP.
abstract: Osmoregulated transporters sense intracellular osmotic pressure and respond to hyperosmotic stress by accumulation of osmolytes to restore normal hydration levels. Here we report the determination of the X-ray structure of a member of the family of betaine/choline/carnitine transporters, the Na(+)-coupled symporter BetP from Corynebacterium glutamicum, which is a highly effective osmoregulated uptake system for glycine betaine. Glycine betaine is bound in a tryptophan box occluded from both sides of the membrane with aromatic side chains lining the transport pathway. BetP has the same overall fold as three unrelated Na(+)-coupled symporters. Whereas these are crystallized in either the outward-facing or the inward-facing conformation, the BetP structure reveals a unique intermediate conformation in the Na(+)-coupled transport cycle. The trimeric architecture of BetP and the break in three-fold symmetry by the osmosensing C-terminal helices suggest a regulatory mechanism of Na(+)-coupled osmolyte transport to counteract osmotic stress.
authors.affiliation: Max Planck Institute of Biophysics, Department of Structural Biology, 60438 Frankfurt am Main, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Ressl
authors.forename: Anke C
authors.initials: AC
authors.lastname: Terwisscha van Scheltinga
authors.forename: Clemens
authors.initials: C
authors.lastname: Vonrhein
authors.forename: Vera
authors.initials: V
authors.lastname: Ott
authors.forename: Christine
authors.initials: C
authors.lastname: Ziegler
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001622:Betaine / Q000378:metabolism*; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D048230:Corynebacterium glutamicum / Q000737:chemistry* / Q000235:genetics; D018360:Crystallography, X-Ray; D017136:Ion Transport; D008958:Models, Molecular; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D012964:Sodium / Q000378:metabolism*; D013329:Structure-Activity Relationship; D027981:Symporters
chemical_list: D001426:Bacterial Proteins; C101652:BetP protein, Corynebacterium glutamicum; D002352:Carrier Proteins; D027981:Symporters; D001622:Betaine; D012964:Sodium