Molecular basis of substrate-induced permeation by an amino acid antiporter

• DOI: 10.1073/pnas.1018081108
• Publication Date: 2011-02-23T03:52:57Z
• Authors: Lukasz Kowalczyk; Mercè Ratera; Antonella Paladino; Paola Bartoccioni; Ekaitz Errasti-Mu...; Eva Valencia; Guillem Portella; Susanna Bial; Antonio Zorzano; Ignacio Fita; Modesto Orozco; Xavier Carpena; José Luis Vázquez...; Manuel Palacín
• Keywords: Conformational change; Structural Biology

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