Prediction of functional residues in water channels and related proteins.
In this paper, we present an updated classification of the ubiquitous MIP (Major Intrinsic Protein) family proteins, including 153 fully or partially sequenced members available in public databases. Presently, about 30 of these proteins have been functionally characterized, exhibiting essentially two distinct types of channel properties: (1) specific water transport by the aquaporins, and (2) small neutral solutes transport, such as glycerol by the glycerol facilitators. Sequence alignments were used to predict amino acids and motifs discriminant in channel specificity. The protein sequences were also analyzed using statistical tools (comparisons of means and correspondence analysis). Five key positions were clearly identified where the residues are specific for each functional subgroup and exhibit high dissimilar physico-chemical properties. Moreover, we have found that the putative channels for small neutral solutes clearly differ from the aquaporins by the amino acid content and the length of predicted loop regions, suggesting a substrate filter function for these loops. From these results, we propose a signature pattern for water transport.
Froger
A
A
UPRES-A CNRS 6026, Biologie Cellulaire et Reproduction, Equipe Canaux et Récepteurs Membranaires, Université de Rennes1 bâtiment 13, France.
Tallur
B
B
Thomas
D
D
Delamarche
C
C
D000818:Animals; D051399:Aquaporin 2; D051400:Aquaporin 3; D051401:Aquaporin 4; D051403:Aquaporin 6; D020346:Aquaporins; D001692:Biological Transport; D005136:Eye Proteins / Q000737:chemistry; D005990:Glycerol / Q000378:metabolism; D006801:Humans; D007473:Ion Channels / Q000737:chemistry* / Q000235:genetics; D008562:Membrane Glycoproteins; D015999:Multivariate Analysis; D016415:Sequence Alignment; D014867:Water / Q000378:metabolism*
C496023:AQP2 protein, human; C496027:AQP3 protein, human; C496030:AQP4 protein, human; D051399:Aquaporin 2; D051401:Aquaporin 4; D051403:Aquaporin 6; D020346:Aquaporins; D005136:Eye Proteins; D007473:Ion Channels; D008562:Membrane Glycoproteins; C030328:aquaporin 0; D014867:Water; D051400:Aquaporin 3; D005990:Glycerol