scholarly journals Structure and function of Helicobacter pylori CagA, the first-identified bacterial protein involved in human cancer

2017 ◽  
Vol 93 (4) ◽  
pp. 196-219 ◽  
Author(s):  
Masanori HATAKEYAMA
Keyword(s):  
Helicobacter Pylori ◽  
Human Cancer ◽  
Structure And Function ◽  
Bacterial Protein ◽  
And Function

scholarly journals Structure and function of the CagA oncoprotein from Helicobacter pylori

2014 ◽  
Vol 70 (a1) ◽  
pp. C839-C839
Author(s):  
Toshiya Senda ◽  
Miki Senda ◽  
Takeru Hayashi ◽  
Masanori Hatakeyama
Keyword(s):  
Helicobacter Pylori ◽  
Plasma Membrane ◽  
Structure And Function ◽  
Terminal Region ◽  
Oncogenic Signaling ◽  
Intrinsically Disordered ◽  
Arginine Residues ◽  
Function Relationship ◽  
Structure And Function Relationship ◽  
And Function

CagA is known as a major bacterial virulence determinant from Helicobacter pylori and is critical for gastric cancer. Upon delivery into the gastric epithelial cells, CagA localizes to the inner leaflet of the plasma membrane and promiscuously interacts with host proteins such as PAR1b and SHP2. The CagA-PAR1-SHP2 complex potentiates oncogenic signaling. Biochemical and physicochemical analyses revealed that CagA is comprises a structured N-terminal region (residues 1-876) and an intrinsically disordered C-terminal region (residues 877-1186). To understand the structure and function relationship of CagA, we determined the crystal structure of the N-terminal region (residues 1-876) of CagA [1]. The N-terminal CagA is rich in α-helices and composed of three domains. Domain I (residues 24-221) is linked to domain II (residues 303-644) by a disordered loop with about 80 amino acid residues. Domain II has a basic patch composed of 14 lysine and 2 arginine residues. Biological experiments revealed that the basic patch mediates the CagA-phosphatidylserine interaction to localize the inner face of the plasma membrane. In addition, we found that C-terminal disordered region forms a lariat-like loop by the interaction between NBS (residues 645 - 824) and CBS (residues 998 - 1038) in the disordered C-terminal region. The formation of the lariat-like loop facilitates promiscuous interaction of CagA with target protein such as SHP2.

scholarly journals Structure and function of efflux pumps that confer resistance to drugs

2003 ◽  
Vol 376 (2) ◽  
pp. 313-338 ◽  
Author(s):  
M. Ines BORGES-WALMSLEY ◽  
Kenneth S. McKEEGAN ◽  
Adrian R. WALMSLEY
Keyword(s):  
Drug Resistance ◽  
Cancer Cells ◽  
Conformational Changes ◽  
Human Cancer ◽  
Efflux Pumps ◽  
Structure And Function ◽  
Drug Efflux ◽  
Diverse Range ◽  
Drug Efflux Pumps ◽  
And Function

Resistance to therapeutic drugs encompasses a diverse range of biological systems, which all have a human impact. From the relative simplicity of bacterial cells, fungi and protozoa to the complexity of human cancer cells, resistance has become problematic. Stated in its simplest terms, drug resistance decreases the chance of providing successful treatment against a plethora of diseases. Worryingly, it is a problem that is increasing, and consequently there is a pressing need to develop new and effective classes of drugs. This has provided a powerful stimulus in promoting research on drug resistance and, ultimately, it is hoped that this research will provide novel approaches that will allow the deliberate circumvention of well understood resistance mechanisms. A major mechanism of resistance in both microbes and cancer cells is the membrane protein-catalysed extrusion of drugs from the cell. Resistant cells exploit proton-driven antiporters and/or ATP-driven ABC (ATP-binding cassette) transporters to extrude cytotoxic drugs that usually enter the cell by passive diffusion. Although some of these drug efflux pumps transport specific substrates, many are transporters of multiple substrates. These multidrug pumps can often transport a variety of structurally unrelated hydrophobic compounds, ranging from dyes to lipids. If we are to nullify the effects of efflux-mediated drug resistance, we must first of all understand how these efflux pumps can accommodate a diverse range of compounds and, secondly, how conformational changes in these proteins are coupled to substrate translocation. These are key questions that must be addressed. In this review we report on the advances that have been made in understanding the structure and function of drug efflux pumps.

scholarly journals Expression of Helicobacter pylori Vacuolating Toxin in Escherichia coli

2003 ◽  
Vol 71 (4) ◽  
pp. 2266-2271 ◽  
Author(s):  
Mark S. McClain ◽  
Timothy L. Cover
Keyword(s):  
Escherichia Coli ◽  
Helicobacter Pylori ◽  
Peptic Ulcer ◽  
Genetic Manipulation ◽  
Expression System ◽  
Structure And Function ◽  
Heterologous Expression System ◽  
Efficient System ◽  
Ulcer Disease ◽  
And Function

ABSTRACT VacA is a secreted toxin that plays a role in Helicobacter pylori colonization of the stomach and that contributes to the pathogenesis of peptic ulcer disease. Studies of VacA structure and function have been hindered by the lack of an efficient system for expression and genetic manipulation of this toxin. In this study, we developed methodology for expression of a functionally active VacA toxin in Escherichia coli. We then used a high-throughput screen to analyze a library of mutant toxins with pentapeptide insertions and identified six mutants that lacked the capacity to induce vacuolation of HeLa cells. The capacity to analyze VacA in this heterologous-expression system should greatly facilitate efforts to elucidate the structure and function of this toxin.

scholarly journals Helicobacter pylori disrupts gastric epithelial barrier structure and function in an MLCK and ROCK dependent fashion

2006 ◽  
Vol 20 (5) ◽  
Author(s):  
Tamia Kateri Lapointe ◽  
Pamela M. O'Connor ◽  
Jason P. Fedwick ◽  
Jon Meddings ◽  
Daniel Menard ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Structure And Function ◽  
Epithelial Barrier ◽  
Barrier Structure ◽  
And Function

scholarly journals Structure and Function of the Bacterial Protein Toxin Phenomycin

Structure ◽  
2020 ◽  
Vol 28 (5) ◽  
pp. 528-539.e9 ◽  
Author(s):  
Bente K. Hansen ◽  
Camilla K. Larsen ◽  
Jakob T. Nielsen ◽  
Esben B. Svenningsen ◽  
Lan B. Van ◽  
...  
Keyword(s):  
Structure And Function ◽  
Bacterial Protein ◽  
Protein Toxin ◽  
And Function
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