Common Challenges in Studying the Structure and Function of Bacterial Proteins: Case Studies from Helicobacter pylori

This paper is an account of the principles and practices of treatment offered at the Cassel Hospital, London, with a particular focus on the Inpatient Families Unit. The Cassel Hospital is an internationally renowned therapeutic community, the operation of which is based on psychoanalytic principles and which has operated within the British National Health Service for nearly 50 years. An account of the historical development of the hospital is given as well as a description of its structure and function. The following three innovative structures are elaborated: a complex network within which patients can develop, Cassel-style nursing care, and nurse-therapist supervision. Theoretical underpinnings are outlined, which together with two case studies facilitate an appreciation of the capacity of the therapeutic network to foster the successful treatment of a range of severely disordered individuals and families. Such treatment may approach a level perhaps otherwise unattainable and which is widely applicable in the public hospital and clinic settings in Australia.

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Structure and function of the CagA oncoprotein from Helicobacter pylori

Acta Crystallographica Section A Foundations and Advances ◽

10.1107/s2053273314091608 ◽

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.

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Structure and function of information centers: Case studies of six organizations

Information & Management ◽

10.1016/0378-7206(87)90011-5 ◽

1987 ◽

Vol 13 (2) ◽

pp. 71-76 ◽

Cited By ~ 8

Author(s):

David P. Christy ◽

Clinton E. White

Keyword(s):

Case Studies ◽

Structure And Function ◽

And Function

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Organic electronics by design: the power of minor atomic and structural changes

Journal of Materials Chemistry C ◽

10.1039/c7tc05052f ◽

2018 ◽

Vol 6 (14) ◽

pp. 3564-3572 ◽

Cited By ~ 16

Author(s):

Brenden McDearmon ◽

Zachariah A. Page ◽

Michael L. Chabinyc ◽

Craig J. Hawker

Keyword(s):

Case Studies ◽

Structural Changes ◽

Electronic Materials ◽

Structure And Function ◽

Structural Variations ◽

Organic Electronic ◽

Design Rules ◽

Fundamental Relationship ◽

Organic Electronic Materials ◽

And Function

Case studies of minor structural variations highlight the fundamental relationship between structure and function to offer design rules with which to develop the next generation of organic electronic materials.

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Expression of Helicobacter pylori Vacuolating Toxin in Escherichia coli

Infection and Immunity ◽

10.1128/iai.71.4.2266-2271.2003 ◽

2003 ◽

Vol 71 (4) ◽

pp. 2266-2271 ◽

Cited By ~ 10

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.

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