Functional and structural characterization of chimeras of a bacterial genotoxin and human type I DNAse

被引:15
作者
DiRienzo, Joseph M. [1 ]
Cao, Linsen [1 ]
Volgina, Alla [1 ]
Bandelac, Georges [2 ]
Korostoff, Jonathan [2 ]
机构
[1] Univ Penn, Sch Dent Med, Dept Microbiol, Philadelphia, PA 19104 USA
[2] Univ Penn, Sch Dent Med, Dept Periodont, Philadelphia, PA 19104 USA
基金
美国国家卫生研究院;
关键词
Aggregatibacter actinomycetemcomitans; chimera; cytolethal distending toxin; epithelial cells; pathogen; type I DNAse; CYTOLETHAL DISTENDING TOXIN; CELL-CYCLE ARREST; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; DEOXYRIBONUCLEASE-I; CYSTIC-FIBROSIS; SUBUNIT; CDTB; INTERNALIZATION; SPECIFICITY; INVOLVEMENT;
D O I
10.1111/j.1574-6968.2008.01457.x
中图分类号
Q93 [微生物学];
学科分类号
071005 [微生物学];
摘要
Chimeras composed of the cdtB gene of a novel bacterial genotoxin and the human type I DNAse I gene were constructed and their products characterized relative to the biochemical and enzymatic properties of the native proteins. The product of a cdtB/DNAse I chimera formed a heterotrimer with the CdtA and CdtC subunits of the genotoxin, and targeted mutations increased the specific activity of the hybrid protein. Expression of active chimeric gene products established that the CdtB protein is an atypical divalent cation-dependent endonuclease and demonstrated the potential for genetically engineering a new class of therapeutic agent for inhibiting the proliferation of cancer cells.
引用
收藏
页码:222 / 231
页数:10
相关论文
共 39 条
[1]
Mechanism of internalization of the cytolethal distending toxin of Actinobacillus actinomycetemcomitans [J].
Akifusa, S ;
Heywood, W ;
Nair, SP ;
Stenbeck, G ;
Henderson, B .
MICROBIOLOGY-SGM, 2005, 151 :1395-1402
[2]
Characterization of point mutations in the cdtA gene of the cytolethal distending toxin of Actinobacillus actinomycetemcomitans [J].
Cao, L ;
Volgina, A ;
Huang, CM ;
Korostoff, J ;
DiRienzo, JM .
MOLECULAR MICROBIOLOGY, 2005, 58 (05) :1303-1321
[3]
Role of aromatic amino acids in receptor binding activity and subunit assembly of the cytolethal distending toxin of Aggregatibacter actinomycetemcomitans [J].
Cao, Linsen ;
Bandelac, Georges ;
Volgina, Alla ;
Korostoff, Jonathan ;
DiRienzo, Joseph M. .
INFECTION AND IMMUNITY, 2008, 76 (07) :2812-2821
[4]
Role of intrachain disulfides in the activities of the CdtA and CdtC subunits of the cytolethal distending toxin of Actinobacillus actinomycetemcomitans [J].
Cao, Linsen ;
Volgina, Alla ;
Korostoff, Jonathan ;
DiRienzo, Joseph M. .
INFECTION AND IMMUNITY, 2006, 74 (09) :4990-5002
[5]
Cao SL, 2004, FEMS MICROBIOL LETT, V237, P97, DOI [10.1111/j.1574-6968.2004.tb09683.x, 10.1016/j.femsle.2004.06.021]
[6]
The cytolethal distending toxin B sub-unit of Helicobacter hepaticus is a Ca2+- and Mg2+-dependent neutral nuclease [J].
Dassanayake, RP ;
Griep, MA ;
Duhamel, GE .
FEMS MICROBIOLOGY LETTERS, 2005, 251 (02) :219-225
[7]
Kinetics of KB and HEp-2 cell responses to an invasive, cytolethal distending toxin-producing strain of Actinobacillus actinomycetemcomitans [J].
DiRienzo, JM ;
Song, M ;
Wan, LSY ;
Ellen, RP .
ORAL MICROBIOLOGY AND IMMUNOLOGY, 2002, 17 (04) :245-251
[8]
Functionally unrelated signalling proteins contain a fold similar to Mg2+-dependent endonucleases [J].
Dlakic, M .
TRENDS IN BIOCHEMICAL SCIENCES, 2000, 25 (06) :272-273
[9]
DNase I homologous residues in CdtB are critical for cytolethal distending toxin-mediated cell cycle arrest [J].
Elwell, CA ;
Dreyfus, LA .
MOLECULAR MICROBIOLOGY, 2000, 37 (04) :952-963
[10]
Study of the cytolethal distending toxin-induced cell cycle arrest in HeLa cells: Involvement of the CDC25 phosphatase [J].
Escalas, N ;
Davezac, N ;
De Rycke, J ;
Baldin, V ;
Mazars, R ;
Ducommun, B .
EXPERIMENTAL CELL RESEARCH, 2000, 257 (01) :206-212