1887

Abstract

Proteins responsible for outer membrane transport across the unique membrane structure of spp. are attractive drug targets in the treatment of human diseases caused by the mycobacterial pathogens, , , and . In contrast with , relatively few outer-membrane proteins (OMPs) have been identified in spp., largely due to the difficulties in isolating mycobacterial membrane proteins and our incomplete understanding of secretion mechanisms and cell wall structure in these organisms. To further expand our knowledge of these elusive proteins in mycobacteria, we have improved upon our previous method of OMP prediction in mycobacteria by taking advantage of genomic data from seven mycobacteria species. Our improved algorithm suggests 4333 sequences as putative OMPs in seven species with varying degrees of confidence. The most virulent pathogenic mycobacterial species are slightly enriched in these selected sequences. We present examples of predicted OMPs involved in horizontal transfer and paralogy expansion. Analysis of local secondary structure content allowed identification of small domains predicted to perform as OMPs; some examples show their involvement in events of tandem duplication and domain rearrangements. We discuss the taxonomic distribution of these discovered families and architectures, often specific to mycobacteria or the wider taxonomic class of . Our results suggest that OMP functionality in mycobacteria is richer than expected and provide a resource to guide future research of these understudied proteins.

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2010-08-01
2019-10-22
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vol. , part 8, pp. 2506 - 2515

Fraction of OMPs remaining after increased restriction of non-Method 1 parameters. Effect of changing the original parameters on OMP prediction in OMP-rich and OMP-poor clusters. Validation of OMP prediction and signal sequence prediction in mycobacteria. OMP scores for known bacterial OMPs. C4, a tandemly repeated OMP domain. ACT, a domain that is duplicated and lost many times. [PDF of figures](242 KB)

Criteria for OMP prediction. [PDF](104 KB)

OMP score for mycobacterial sequences. This file provides the results of the different scores and tests for protein sequences of seven mycobacteria used in this manuscript (30605 sequences of length 50 amino acids or more). Each row represents a sequence. The columns indicate (1) cluster ID, (2) species, (3) gene identifier, (4) OMP score, (5) Frac, (6) PerBeta, (7) Smean, (8) Dval (from Tat), (9) number of predicted beta strands of five residues or longer and (10) number of residues in those, (11) number of predicted transmembrane helices, (12) position of the first transmembrane helix, (13) length of the sequence, (14) computed pI, (15) number of cysteines. Columns 16–21 are regarding the properties found on a 300 aa window whose position was selected as described in Methods: (16) window left start position, (17) number of beta strands of five residues or more, (18) residues in those, (19) percentage of beta structure predicted and (20) Frac inside the 300 amino acid window, and (21) window beta score. [Excel file](8.6 MB)



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