3OB6

Structure of AdiC(N101A) in the open-to-out Arg+ bound conformation

Summary for 3OB6

• Entry DOI: 10.2210/pdb3ob6/pdb
• Descriptor: AdiC arginine:agmatine antiporter, ARGININE (2 entities in total)
• Functional Keywords: amino acid antiporter, arginine, membrane, transmembrane antiporter, apc-t, 5+5 inverted repeat, membrane protein
• Biological source: Escherichia coli
• Total number of polymer chains: 2
• Total formula weight: 94002.89

Authors

Carpena, X.,Kowalczyk, L.,Ratera, M.,Valencia, E.,Vazquez-lbar, J.L.,Fita, I.,Palacin, M. (deposition date: 2010-08-06, release date: 2011-03-16, Last modification date: 2023-09-06)

Primary citation

Kowalczyk, L.,Ratera, M.,Paladino, A.,Bartoccioni, P.,Errasti-Murugarren, E.,Valencia, E.,Portella, G.,Bial, S.,Zorzano, A.,Fita, I.,Orozco, M.,Carpena, X.,Vazquez-Ibar, J.L.,Palacin, M.
Molecular basis of substrate-induced permeation by an amino acid antiporter.
Proc.Natl.Acad.Sci.USA, 108:3935-3940, 2011

PubMed Abstract: Transporters of the amino acid, polyamine and organocation (APC) superfamily play essential roles in cell redox balance, cancer, and aminoacidurias. The bacterial L-arginine/agmatine antiporter, AdiC, is the main APC structural paradigm and shares the "5 + 5 inverted repeat" fold found in other families like the Na(+)-coupled neurotransmitter transporters. The available AdiC crystal structures capture two states of its transport cycle: the open-to-out apo and the outward-facing Arg(+)-bound occluded. However, the role of Arg(+) during the transition between these two states remains unknown. Here, we report the crystal structure at 3.0 Å resolution of an Arg(+)-bound AdiC mutant (N101A) in the open-to-out conformation, completing the picture of the major conformational states during the transport cycle of the 5 + 5 inverted repeat fold-transporters. The N101A structure is an intermediate state between the previous known AdiC conformations. The Arg(+)-guanidinium group in the current structure presents high mobility and delocalization, hampering substrate occlusion and resulting in a low translocation rate. Further analysis supports that proper coordination of this group with residues Asn101 and Trp293 is required to transit to the occluded state, providing the first clues on the molecular mechanism of substrate-induced fit in a 5 + 5 inverted repeat fold-transporter. The pseudosymmetry found between repeats in AdiC, and in all fold-related transporters, restraints the conformational changes, in particular the transmembrane helices rearrangements, which occur during the transport cycle. In AdiC these movements take place away from the dimer interface, explaining the independent functioning of each subunit.

PubMed: 21368142
DOI: 10.1073/pnas.1018081108

Experimental method

X-RAY DIFFRACTION (3 Å)