Molecular basis of transport and regulation in the Na(+)/betaine symporter BetP

Nature. 2009 Mar 5;458(7234):47-52. doi: 10.1038/nature07819.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Betaine / metabolism*
  • Binding Sites
  • Carrier Proteins / chemistry*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Corynebacterium glutamicum / chemistry*
  • Corynebacterium glutamicum / genetics
  • Crystallography, X-Ray
  • Ion Transport
  • Models, Molecular
  • Protein Binding
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary
  • Sodium / metabolism*
  • Structure-Activity Relationship
  • Symporters


  • Bacterial Proteins
  • BetP protein, Corynebacterium glutamicum
  • Carrier Proteins
  • Symporters
  • Betaine
  • Sodium

Associated data

  • PDB/2W8A