Large-scale survey for potentially targetable indels in bacterial and protozoan proteins

被引:18
作者
Cherkasov, A
Lee, SJ
Nandan, D
Reiner, NE
机构
[1] Univ British Columbia, Fac Med, Dept Med, Div Infect Dis, Vancouver, BC V5Z 3J5, Canada
[2] Univ British Columbia, Fac Sci, Dept Med, Div Infect Dis, Vancouver, BC V5Z 3J5, Canada
[3] Vancouver Coastal Hlth Res Inst, Vancouver, BC, Canada
[4] Univ British Columbia, Strateg Training Program Bioinformat, Fac Med, Vancouver, BC V5Z 1M9, Canada
[5] Univ British Columbia, Strateg Training Program Bioinformat, Fac Sci, Vancouver, BC V5Z 1M9, Canada
关键词
homology modeling; protein length polymorphism; indels; virulence; protozoa;
D O I
10.1002/prot.20631
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Our previous results demonstrated that some essential, housekeeping proteins from pathogenic microorganisms may contain sizable insertions-deletions in their sequences (compared to close human homologs) that can be responsible for unexpected virulence properties. For example, we found that indel-bearing elongation factor-1 alpha from several pathogenic protozoa can activate a human tyrosine phosphatase SHP-1 leading to deactivation of macrophages. On the one hand, these findings allowed development of a strategy for targeting some indel-containing pathogen proteins that have similar human counterparts. On the other hand, the results raised numerous questions regarding the nature and implications of sequence indels in pathogen proteins. In the present study, we conducted a large-scale survey of indels in proteins from 136 bacterial and protozoan genomes. It has been established that sizable insertions and deletions occur in approximately 5-10% of bacterial proteins with close human homologs, while proteins from the protozoan pathogens such as Trypanosoma cruzi, Plasmodium falciparum, and Leishmania donovani exhibit elevated indel content that can reach up to 25%. The finding suggested that the occurrence of sequence indels may be involved in the evolution of pathogenic mechanisms in these protozoa.
引用
收藏
页码:371 / 380
页数:10
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