CotG-Like Modular Proteins Are Common among Spore-Forming Bacilli

ABSTRACTCotG is an abundant protein initially identified as an outer component of theBacillus subtilisspore coat. It has an unusual structure characterized by several repeats of positively charged amino acids that are probably the outcome of multiple rounds of gene elongation events in an ancestral minigene. CotG is not highly conserved, and its orthologues are present in only twoBacillusand twoGeobacillusspecies. InB. subtilis, CotG is the target of extensive phosphorylation by a still unidentified enzyme and has a role in the assembly of some outer coat proteins. We report now that most spore-forming bacilli contain a protein not homologous to CotG ofB. subtilisbut sharing a central “modular” region defined by a pronounced positive charge and randomly coiled tandem repeats. Conservation of the structural features in most spore-forming bacilli suggests a relevant role for the CotG-like protein family in the structure and function of the bacterial endospore. To expand our knowledge on the role of CotG, we dissected theB. subtilisprotein by constructing deletion mutants that express specific regions of the protein and observed that they have different roles in the assembly of other coat proteins and in spore germination.IMPORTANCECotG ofB. subtilisis not highly conserved in theBacillusgenus; however, a CotG-like protein with a modular structure and chemical features similar to those of CotG is common in spore-forming bacilli, at least when CotH is also present. The conservation of CotG-like features when CotH is present suggests that the two proteins act together and may have a relevant role in the structure and function of the bacterial endospore. Dissection of the modular composition of CotG ofB. subtilisby constructing mutants that express only some of the modules has allowed a first characterization of CotG modules and will be the basis for a more detailed functional analysis.

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Structure and Function of Glycosylated Tandem Repeats from Candida albicans Als Adhesins

Eukaryotic Cell ◽

10.1128/ec.00235-09 ◽

2009 ◽

Vol 9 (3) ◽

pp. 405-414 ◽

Cited By ~ 38

Author(s):

Aaron T. Frank ◽

Caleen B. Ramsook ◽

Henry N. Otoo ◽

Cho Tan ◽

Gregory Soybelman ◽

...

Keyword(s):

Candida Albicans ◽

Tandem Repeats ◽

Cell Aggregation ◽

Structure And Function ◽

Hydrophobic Surfaces ◽

Content Type ◽

Domain Structures ◽

Aggregation Activity ◽

Fungal Adhesins ◽

And Function

ABSTRACT Tandem repeat (TR) regions are common in yeast adhesins, but their structures are unknown, and their activities are poorly understood. TR regions in Candida albicans Als proteins are conserved glycosylated 36-residue sequences with cell-cell aggregation activity (J. M. Rauceo, R. De Armond, H. Otoo, P. C. Kahn, S. A. Klotz, N. K. Gaur, and P. N. Lipke, Eukaryot. Cell 5:1664–1673, 2006). Ab initio modeling with either Rosetta or LINUS generated consistent structures of three-stranded antiparallel β-sheet domains, whereas randomly shuffled sequences with the same composition generated various structures with consistently higher energies. O- and N-glycosylation patterns showed that each TR domain had exposed hydrophobic surfaces surrounded by glycosylation sites. These structures are consistent with domain dimensions and stability measurements by atomic force microscopy (D. Alsteen, V. Dupres, S. A. Klotz, N. K. Gaur, P. N. Lipke, and Y. F. Dufrene, ACS Nano 3:1677–1682, 2009) and with circular dichroism determination of secondary structure and thermal stability. Functional assays showed that the hydrophobic surfaces of TR domains supported binding to polystyrene surfaces and other TR domains, leading to nonsaturable homophilic binding. The domain structures are like “classic” subunit interaction surfaces and can explain previously observed patterns of promiscuous interactions between TR domains in any Als proteins or between TR domains and surfaces of other proteins. Together, the modeling techniques and the supporting data lead to an approach that relates structure and function in many kinds of repeat domains in fungal adhesins.

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Cysteine-Free Proteins in the Immunobiology of Arthropod-Borne Diseases

Journal of Biomedicine and Biotechnology ◽

10.1155/2010/171537 ◽

2010 ◽

Vol 2010 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

J. Santiago Mejia ◽

Erik N. Arthun ◽

Richard G. Titus

Keyword(s):

Plasmodium Falciparum ◽

Amino Acid ◽

Distribution Patterns ◽

Structural Features ◽

Structure And Function ◽

Cysteine Residues ◽

Distribution Analysis ◽

And Function ◽

Abundance And Distribution ◽

Host Parasite

One approach to identify epitopes that could be used in the design of vaccines to control several arthropod-borne diseases simultaneously is to look for common structural features in the secretome of the pathogens that cause them. Using a novel bioinformatics technique, cysteine-abundance and distribution analysis, we found that many different proteins secreted by several arthropod-borne pathogens, includingPlasmodium falciparum, Borrelia burgdorferi, and eight species of Proteobacteria, are devoid of cysteine residues. The identification of three cysteine-abundance and distribution patterns in several families of proteins secreted by pathogenic and nonpathogenic Proteobacteria, and not found when the amino acid analyzed was tryptophan, provides evidence of forces restricting the content of cysteine residues in microbial proteins during evolution. We discuss these findings in the context of protein structure and function, antigenicity and immunogenicity, and host-parasite relationships.

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Reflections on team culture, structure and function of an intensive support service centred on positive behavioural support

Tizard Learning Disability Review ◽

10.1108/tldr-01-2016-0003 ◽

2016 ◽

Vol 21 (4) ◽

pp. 203-211 ◽

Cited By ~ 1

Author(s):

Lawrence A. Patterson ◽

Samuel Berry

Keyword(s):

Social Services ◽

Support Service ◽

Structure And Function ◽

Content Type ◽

Case Examples ◽

Behavioural Support ◽

Team Culture ◽

Shared Identity ◽

The Right ◽

And Function

Purpose The purpose of this paper is to explore experiences of team culture, structure and function of an intensive support service (ISS) within the context of the recent service guidance “Building the Right Support” (NHS England, Local Government Association and Association of Directors of Adult Social Services, 2015). Reflections on the Hampshire and Southampton ISS set up in 2010 are discussed with a view to informing a debate about frameworks for ISS services nationally. Design/methodology/approach A reflective piece, drawing on experience and case examples. Findings This paper describes that a key function of an ISS is making individuals safe and this is significantly assisted by using shared team formulation, which can enable information and perspectives to be shared between and within teams as rapidly as possible. Further, a case is made for recognising the importance of inter-disciplinary practice, as the Southampton and Hampshire ISS has removed the “old fashioned” demarcations that led to individuals seeing a “procession” of different professionals from different disciplines. This relates to team structure, but importantly is about a culture of holding a shared identity based on positive behavioural support values, rather than a traditional uni-disciplinary perspective. Practical implications ISS models are being proposed by NHS England and this paper suggests some important practical aspects. Originality/value Limited literature exists examining the team culture within ISSs, which contributes to desired outcomes for service users. This paper opens a debate about structural and functional aspects of service delivery in this service model.

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In silico prediction of structure and function for a large family of transmembrane proteins that includes human Tmem41b

F1000Research ◽

10.12688/f1000research.27676.1 ◽

2020 ◽

Vol 9 ◽

pp. 1395

Author(s):

Shahram Mesdaghi ◽

David L. Murphy ◽

Filomeno Sánchez Rodríguez ◽

J. Javier Burgos-Mármol ◽

Daniel J. Rigden

Keyword(s):

Ab Initio ◽

Rotational Symmetry ◽

Domain Boundary ◽

Pfam Domain ◽

Transmembrane Proteins ◽

Large Family ◽

Data Bank ◽

Structural Features ◽

Structure And Function ◽

And Function

Background: Recent strides in computational structural biology have opened up an opportunity to understand previously uncharacterised proteins. The under-representation of transmembrane proteins in the Protein Data Bank highlights the need to apply new and advanced bioinformatics methods to shed light on their structure and function. This study focuses on a family of transmembrane proteins containing the Pfam domain PF09335 ('SNARE_ASSOC'/ ‘VTT ‘/’Tvp38’). One prominent member, Tmem41b, has been shown to be involved in early stages of autophagosome formation and is vital in mouse embryonic development as well as being identified as a viral host factor of SARS-CoV-2. Methods: We used evolutionary covariance-derived information to construct and validate ab initio models, make domain boundary predictions and infer local structural features. Results: The results from the structural bioinformatics analysis of Tmem41b and its homologues showed that they contain a tandem repeat that is clearly visible in evolutionary covariance data but much less so by sequence analysis. Furthermore, cross-referencing of other prediction data with covariance analysis showed that the internal repeat features two-fold rotational symmetry. Ab initio modelling of Tmem41b and homologues reinforces these structural predictions. Local structural features predicted to be present in Tmem41b were also present in Cl-/H+ antiporters. Conclusions: The results of this study strongly point to Tmem41b and its homologues being transporters for an as-yet uncharacterised substrate and possibly using H+ antiporter activity as its mechanism for transport.

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Campylobacter jejuni Triggers Signaling through Host Cell Focal Adhesions To Inhibit Cell Motility

mBio ◽

10.1128/mbio.01494-21 ◽

2021 ◽

Author(s):

Courtney M. Klappenbach ◽

Nicholas M. Negretti ◽

Jesse Aaron ◽

Teng-Leong Chew ◽

Michael E. Konkel

Keyword(s):

Epithelial Cells ◽

Cell Motility ◽

Host Cell ◽

Campylobacter Jejuni ◽

Focal Adhesion ◽

Foodborne Pathogen ◽

Focal Adhesions ◽

Structure And Function ◽

Content Type ◽

And Function

Campylobacter jejuni is a major foodborne pathogen that causes severe gastritis. We investigated the dynamics of focal adhesion structure and function in C. jejuni -infected epithelial cells.

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Structural Features of a Bacteroidetes-Affiliated Cellulase Linked with a Polysaccharide Utilization Locus

Scientific Reports ◽

10.1038/srep11666 ◽

2015 ◽

Vol 5 (1) ◽

Cited By ~ 14

Author(s):

A.E. Naas ◽

A.K. MacKenzie ◽

B. Dalhus ◽

V.G.H. Eijsink ◽

P.B. Pope

Keyword(s):

Active Site ◽

Three Dimensional ◽

Structural Features ◽

Structure And Function ◽

Dimensional Structure ◽

Active Site Cleft ◽

Polysaccharide Utilization Locus ◽

And Function ◽

Rumen Metagenome

Abstract Previous gene-centric analysis of a cow rumen metagenome revealed the first potentially cellulolytic polysaccharide utilization locus, of which the main catalytic enzyme (AC2aCel5A) was identified as a glycoside hydrolase (GH) family 5 endo-cellulase. Here we present the 1.8 Å three-dimensional structure of AC2aCel5A and characterization of its enzymatic activities. The enzyme possesses the archetypical (β/α)8-barrel found throughout the GH5 family and contains the two strictly conserved catalytic glutamates located at the C-terminal ends of β-strands 4 and 7. The enzyme is active on insoluble cellulose and acts exclusively on linear β-(1,4)-linked glucans. Co-crystallization of a catalytically inactive mutant with substrate yielded a 2.4 Å structure showing cellotriose bound in the −3 to −1 subsites. Additional electron density was observed between Trp178 and Trp254, two residues that form a hydrophobic “clamp”, potentially interacting with sugars at the +1 and +2 subsites. The enzyme’s active-site cleft was narrower compared to the closest structural relatives, which in contrast to AC2aCel5A, are also active on xylans, mannans and/or xyloglucans. Interestingly, the structure and function of this enzyme seem adapted to less-substituted substrates such as cellulose, presumably due to the insufficient space to accommodate the side-chains of branched glucans in the active-site cleft.

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IX. On the structure and development of the liver

Philosophical Transactions of the Royal Society of London ◽

10.1098/rstl.1849.0009 ◽

1849 ◽

Vol 139 ◽

pp. 109-137 ◽

Cited By ~ 1

Keyword(s):

Royal Society ◽

A Priori ◽

Structural Features ◽

Structure And Function ◽

Conclusive Evidence ◽

Interesting Paper ◽

Biliary Ducts ◽

And Function ◽

Do So

In venturing to offer a second communication to the Royal Society respecting the structure of the liver, I feel the rather anxious to do so, that I may have an opportunity of correcting an error and supplying a deficiency which existed in my previous paper. In the following observations I purpose to present some account of the structure of the liver examined in the ascending series of animals, and also to describe the several stages of its evolution in the embryo; in this way I trust I may be able to exhibit the characteristic structural features of the organ as it exists in Man and the higher animals, and also to determine the true place which ought to be assigned to it in a classification of the various glandular organs occurring in the same. I am not aware that any detailed account of the structure of the liver has been recently published, except that by M. Natalis Guillot, which however, so far as I comprehend it, does not seem to be one that can be readily accepted; the idea that the minute biliary ducts and lymphatics originate together in a common net-work, is à priori improbable, and entirely opposed to conclusive evidence (as I think), which will be subsequently adduced. A very interesting paper on the structure and function of the liver has also appeared in the 4th volume of the Guy’s Hospital Reports, from the pen of Dr. Williams; to his labours I shall several times have occasion to refer, but it will be seen that I differ from him in several particulars, especially respecting the importance of the basement or limitary membrane.

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Bacterial ß-Barrel Outer Membrane Proteins

Handbook of Research on Systems Biology Applications in Medicine ◽

10.4018/978-1-60566-076-9.ch010 ◽

2009 ◽

pp. 182-207

Author(s):

Pantelis G. Bagos ◽

Stavros J. Hamodrakas

Keyword(s):

Membrane Proteins ◽

Outer Membrane ◽

Bacterial Cell ◽

Outer Membrane Proteins ◽

Structural Features ◽

Structure And Function ◽

Structural Motif ◽

Functional Roles ◽

Bacterial Outer Membrane ◽

And Function

ß-barrel outer membrane proteins constitute the second and less well-studied class of transmembrane proteins. They are present exclusively in the outer membrane of Gram-negative bacteria and presumably in the outer membrane of mitochondria and chloroplasts. During the last few years, remarkable advances have been made towards an understanding of their functional and structural features. It is now wellknown that ß-barrels are performing a large variety of biologically important functions for the bacterial cell. Such functions include acting as specific or non-specific channels, receptors for various compounds, enzymes, translocation channels, structural proteins, and adhesion proteins. All these functional roles are of great importance for the survival of the bacterial cell under various environmental conditions or for the pathogenic properties expressed by these organisms. This chapter reviews the currently available literature regarding the structure and function of bacterial outer membrane proteins. We emphasize the functional diversity expressed by a common structural motif such as the ß-barrel, and we provide evidence from the current literature for dozens of newly discovered families of transmembrane ß-barrels.

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Regulation of OmpA Translation and Shigella dysenteriae Virulence by an RNA Thermometer

Infection and Immunity ◽

10.1128/iai.00871-19 ◽

2019 ◽

Vol 88 (3) ◽

Cited By ~ 1

Author(s):

Erin R. Murphy ◽

Johanna Roßmanith ◽

Jacob Sieg ◽

Megan E. Fris ◽

Hebaallaha Hussein ◽

...

Keyword(s):

In Silico ◽

Bacterial Species ◽

Regulation Of Gene Expression ◽

Structure And Function ◽

Shigella Dysenteriae ◽

Content Type ◽

Bacterial Physiology ◽

Wide Range ◽

Rna Thermometer ◽

And Function

ABSTRACT RNA thermometers are cis-acting riboregulators that mediate the posttranscriptional regulation of gene expression in response to environmental temperature. Such regulation is conferred by temperature-responsive structural changes within the RNA thermometer that directly result in differential ribosomal binding to the regulated transcript. The significance of RNA thermometers in controlling bacterial physiology and pathogenesis is becoming increasingly clear. This study combines in silico, molecular genetics, and biochemical analyses to characterize both the structure and function of a newly identified RNA thermometer within the ompA transcript of Shigella dysenteriae. First identified by in silico structural predictions, genetic analyses have demonstrated that the ompA RNA thermometer is a functional riboregulator sufficient to confer posttranscriptional temperature-dependent regulation, with optimal expression observed at the host-associated temperature of 37°C. Structural studies and ribosomal binding analyses have revealed both increased exposure of the ribosomal binding site and increased ribosomal binding to the ompA transcript at permissive temperatures. The introduction of site-specific mutations predicted to alter the temperature responsiveness of the ompA RNA thermometer has predictable consequences for both the structure and function of the regulatory element. Finally, in vitro tissue culture-based analyses implicate the ompA RNA thermometer as a bona fide S. dysenteriae virulence factor in this bacterial pathogen. Given that ompA is highly conserved among Gram-negative pathogens, these studies not only provide insight into the significance of riboregulation in controlling Shigella virulence, but they also have the potential to facilitate further understanding of the physiology and/or pathogenesis of a wide range of bacterial species.

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Commentary on “Reflections on culture, structure and function of an intensive support service centred on positive behavioural support”

Tizard Learning Disability Review ◽

10.1108/tldr-06-2016-0018 ◽

2016 ◽

Vol 21 (4) ◽

pp. 212-219 ◽

Cited By ~ 2

Author(s):

Sandy Toogood

Keyword(s):

Support Service ◽

Structure And Function ◽

Content Type ◽

Behavioural Support ◽

Wide Range ◽

Service Models ◽

History Of ◽

Positive Behaviour Support ◽

The Uk ◽

And Function

Purpose The purpose of this paper is to provide a commentary on Patterson and Berry’s paper “Reflections on culture, structure and function of an intensive support service centred on positive behavioural support”. Design/methodology/approach This paper reviews key ideas presented in Patterson and Berry’s article relative to the recent history of service delivery in the UK and the growing interest being shown in positive behaviour support. Findings Patterson and Berry’s article adds to a modest literature on specialist support services and should stimulate further descriptions of service models and the concepts underpinning them. Originality/value The literature on specialist support service models is limited and this addition should be relevant to a wide range of clinicians, consumers and commissioners.

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