GIBBS MOTIF SAMPLING - DETECTION OF BACTERIAL OUTER-MEMBRANE PROTEIN REPEATS

The detection and alignment of locally conserved regions (motifs) in m ultiple sequences can provide insight into protein structure, function , and evolution. A new Gibbs sampling algorithm is described that dete cts motif-encoding regions in sequences and optimally partitions them into distinct motif models; this is illustrated using a set of immunog lobulin fold proteins. When applied to sequences sharing a single moti f, the sampler can be used to classify motif regions into related subm odels, as is illustrated using helix-turn-helix DNA-binding proteins. Other statistically based procedures are described for searching a dat abase for sequences matching motifs found by the sampler. When applied to a set of 32 very distantly related bacterial integral outer membra ne proteins, the sampler revealed that they share a subtle, repetitive motif. Although BLAST (Altschul SF et al., 1990, J Mol Biol 215:403-4 10) fails to detect significant pairwise similarity between any of the sequences, the repeats present in these outer membrane proteins, take n as a whole, are highly significant (based on a generally applicable statistical test for motifs described here). Analysis of bacterial por ins with known trimeric beta-barrel structure and related proteins rev eals a similar repetitive motif corresponding to alternating membrane- spanning beta-strands. These beta-strands occur on the membrane interf ace (as opposed to the trimeric interface) of the beta-barrel. The bro ad conservation and structural location of these repeats suggests that they play important functional roles.