Structure of the formate transporter FocA reveals a pentameric aquaporin-like channel

• Published in: Nature (London) 2009-11, Vol.462 (7272), p.467-472
• Main Authors: Wang, Yi, Huang, Yongjian, Wang, Jiawei, Cheng, Chao, Huang, Weijiao, Lu, Peilong, Xu, Ya-Nan, Wang, Pengye, Yan, Nieng, Shi, Yigong
• Format: Article
• Language: English
• Subjects: Acids; Algae; Aquaporins; Aquaporins - chemistry; Aquaporins - metabolism; Archaea; Bacteria; Carboxylases; Channels; Crystallography, X-Ray; E coli; Energy conservation; Escherichia coli; Escherichia coli - chemistry; Escherichia coli - genetics; Escherichia coli - metabolism; Escherichia coli Proteins - chemistry; Escherichia coli Proteins - genetics; Escherichia coli Proteins - metabolism; Evolution; Formates; Formates - metabolism; Fungi; Humanities and Social Sciences; Liposomes - chemistry; Liposomes - metabolism; Membrane Transport Proteins - chemistry; Membrane Transport Proteins - genetics; Membrane Transport Proteins - metabolism; Models, Molecular; Molecular Mimicry; Molecules; multidisciplinary; Mutation; Parasites; Permeability; Properties; Protein Structure, Quaternary; Proteins; Science; Science (multidisciplinary); Structural analysis; Structure; Structure-Activity Relationship; Transport; Transporter; Water - analysis; Water - metabolism
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature08610

FocA is a representative member of the formate–nitrite transporter family, which transports short-chain acids in bacteria, archaea, fungi, algae and parasites. The structure and transport mechanism of the formate–nitrite transporter family remain unknown. Here we report the crystal structure of Escherichia coli FocA at 2.25 Å resolution. FocA forms a symmetric pentamer, with each protomer consisting of six transmembrane segments. Despite a lack of sequence homology, the overall structure of the FocA protomer closely resembles that of aquaporin and strongly argues that FocA is a channel, rather than a transporter. Structural analysis identifies potentially important channel residues, defines the channel path and reveals two constriction sites. Unlike aquaporin, FocA is impermeable to water but allows the passage of formate. A structural and biochemical investigation provides mechanistic insights into the channel activity of FocA. FocA transporter: channel vision FocA is a member of the formate–nitrite transporter family, which transports short-chain acids in bacteria, archaea, fungi, algae and parasites. Now the X-ray crystal structure of FocA has been determined at 2.25 Å resolution. The transporter is found to form a symmetric pentamer, with the overall structure of the FocA protomer closely resembling that of aquaporin. This suggests that FocA is in fact a channel, rather than a transporter. The formate–nitrite transporter family, of which FocA is a representative member, is known to transport short-chain acids in bacteria, archaea, fungi, algae and parasites; however, the structure and transport mechanism of these transporters remain unknown. Here, study of the crystal structure of Escherichia coli FocA reveals that the overall structure of FocA closely resembles that of aquaporin, suggesting that it is in fact a channel, rather than a transporter.