Predictive evidence for a porin-type β-barrel fold in CHIP28 and other members of the MIP family. A restricted-pore model common to water channels and facilitators

Fischbarg, J.; Li, J.; Cheung, M.; Czegledy, F.; Iserovich, P.; Kuang, K.

Water channels are the subject of much current attention, as they may be central for cell functions in a host of tissues. We have analyzed the possible fold of facilitators and water channels of the MIP family based on structural predictions, on findings about the topology of CHIP28, and on the biophysical characteristics of water channels. We developed predictions for the following proteins: MIP26, NOD26, GLP, BIB, γ-TIP, FA-CHIP, CHIP28k, WCH-CD1, and CHIP28. We utilized Kyte Doolittle hydrophobicity, Eisenberg's amphiphilicity, Chou-Fasman-Prevelige propensities, and our own Union algorithm. We found that hydrophobic amphiphilic segments likely to be transmembrane were consistently shorter than required for α-helical segments, but of the correct length for β-strands. Turn propensity was high at frequent intervals, consistent with transmembrane β-strands. We propose that these proteins fold as porin-like 16-stranded antiparallel β-barrels. In water channels, from the size of molecules excluded, an extramembrane loop(s) would enter the pore and restrict it to a bottleneck with a width 4 Å ⩽w ⩽5 Å. A similar but more mobile loop(s) would act as gate and binding site for the facilitators of the MIP family.