title: Are most transporters and channels beta barrels?
abstract: Given the sequence of transporters or channels of unknown secondary structure, it is usual to predict their putative transmembrane regions as alpha-helical. However, recent evidence for a facilitative glucose transporter (GLUT1) appears inconsistent with such predictions, which has led us to propose an alternative folding model for GLUTs based on the 16-stranded antiparallel beta-barrel of porins. Here we apply the same predictive algorithms we used for GLUTs to several other membrane proteins. For some of them, a high-resolution structure has been derived (beta-barrels: Rhodobacter capsulatus and Escherichia coli porins; multihelical: colicin A, bacteriorhodopsin, and reaction center L chain); we use them to test the prediction procedures. The other proteins we analyze (GLUT1, CHIP28, acetylcholine receptor alpha subunit, lac permease, Na(+)-glucose cotransporter, shaker K+ channel, sarcoplasmic reticulum Ca(2+)-ATPase) are representative of classes of similar membrane proteins. As with GLUTs, we find that the predicted transmembrane segments of these proteins are consistently shorter than expected for transmembrane spanning alpha-helices, but are of the correct length and number for the proteins to fold instead as porin-like beta-barrels.
authors.affiliation: Department of Physiology and Cellular Biophysics, College of Physicians and Surgeons, Columbia University, New York, NY 10032.
authors.forename: J
authors.initials: J
authors.lastname: Fischbarg
authors.forename: M
authors.initials: M
authors.lastname: Cheung
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: P
authors.initials: P
authors.lastname: Iserovich
authors.forename: F
authors.initials: F
authors.lastname: Czegledy
authors.forename: K
authors.initials: K
authors.lastname: Kuang
authors.forename: M
authors.initials: M
authors.lastname: Garner
mesh_terms: D000465:Algorithms; D000818:Animals; D051398:Aquaporin 1; D020346:Aquaporins; D001426:Bacterial Proteins / Q000737:chemistry*; D000252:Calcium-Transporting ATPases / Q000737:chemistry; D002352:Carrier Proteins / Q000737:chemistry*; D002462:Cell Membrane / Q000378:metabolism; D004926:Escherichia coli / Q000737:chemistry; D029968:Escherichia coli Proteins; D051272:Glucose Transporter Type 1; D007473:Ion Channels / Q000737:chemistry*; D026901:Membrane Transport Proteins / Q000737:chemistry; D009004:Monosaccharide Transport Proteins / Q000737:chemistry; D018272:Porins / Q000737:chemistry; D017433:Protein Structure, Secondary; D011950:Receptors, Cholinergic / Q000737:chemistry; D016354:Rhodobacter capsulatus / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000201:enzymology; D027981:Symporters
chemical_list: D020346:Aquaporins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D029968:Escherichia coli Proteins; D051272:Glucose Transporter Type 1; D007473:Ion Channels; C050221:LacY protein, E coli; D026901:Membrane Transport Proteins; D009004:Monosaccharide Transport Proteins; D018272:Porins; D011950:Receptors, Cholinergic; D027981:Symporters; D051398:Aquaporin 1; C021499:lactose permease; D000252:Calcium-Transporting ATPases