Molecular basis of transport and regulation in the Na(+)/betaine symporter BetP.
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.
Ressl
Susanne
S
Max Planck Institute of Biophysics, Department of Structural Biology, 60438 Frankfurt am Main, Germany.
Terwisscha van Scheltinga
Anke C
AC
Vonrhein
Clemens
C
Ott
Vera
V
Ziegler
Christine
C
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
D001426:Bacterial Proteins; C101652:BetP protein, Corynebacterium glutamicum; D002352:Carrier Proteins; D027981:Symporters; D001622:Betaine; D012964:Sodium