4DOJ

Crystal structure of BetP in outward-facing conformation

Summary for 4DOJ

• Entry DOI: 10.2210/pdb4doj/pdb
• Descriptor: Glycine betaine transporter BetP, CHLORIDE ION, (1S)-2-{[{[(2R)-2,3-DIHYDROXYPROPYL]OXY}(HYDROXY)PHOSPHORYL]OXY}-1-[(PALMITOYLOXY)METHYL]ETHYL STEARATE, ... (5 entities in total)
• Functional Keywords: transport protein
• Biological source: Corynebacterium glutamicum
• Cellular location: Cell membrane; Multi-pass membrane protein: P54582
• Total number of polymer chains: 3
• Total formula weight: 184629.93

Authors

Perez, C.,Ziegler, C. (deposition date: 2012-02-09, release date: 2012-06-06, Last modification date: 2024-02-28)

Primary citation

Perez, C.,Koshy, C.,Yildiz, O.,Ziegler, C.
Alternating-access mechanism in conformationally asymmetric trimers of the betaine transporter BetP.
Nature, 490:126-130, 2012

PubMed Abstract: Betaine and Na(+) symport has been extensively studied in the osmotically regulated transporter BetP from Corynebacterium glutamicum, a member of the betaine/choline/carnitine transporter family, which shares the conserved LeuT-like fold of two inverted structural repeats. BetP adjusts its transport activity by sensing the cytoplasmic K(+) concentration as a measure for hyperosmotic stress via the osmosensing carboxy-terminal domain. BetP needs to be in a trimeric state for communication between individual protomers through several intratrimeric interaction sites. Recently, crystal structures of inward-facing BetP trimers have contributed to our understanding of activity regulation on a molecular level. Here we report new crystal structures, which reveal two conformationally asymmetric BetP trimers, capturing among them three distinct transport states. We observe a total of four new conformations at once: an outward-open apo and an outward-occluded apo state, and two closed transition states--one in complex with betaine and one substrate-free. On the basis of these new structures, we identified local and global conformational changes in BetP that underlie the molecular transport mechanism, which partially resemble structural changes observed in other sodium-coupled LeuT-like fold transporters, but show differences we attribute to the osmolytic nature of betaine, the exclusive substrate specificity and the regulatory properties of BetP.

PubMed: 22940865
DOI: 10.1038/nature11403

Experimental method

X-RAY DIFFRACTION (3.25 Å)