3D structure of a <i>Brucella melitensis</i> porin: molecular modelling in lipid membranes

Lopes-Rodrigues, Maximilien; Zanuy, David; Alemán, Carlos; Michaux, Catherine; Perpète, Éric A.

doi:10.1080/07391102.2018.1529627

Cited by 6 publications

(5 citation statements)

References 64 publications

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“…Since these loop regions in β-barrel or the surface-exposed globular domain of OMP plays important role in oligomerization states 45 , and here also the surface-exposed globular domain likely contributes to dimer formation. Some of the hypothetical proteins (K74_10375, K747_09130, and K747_06625) and outer membrane protein is associated with biofilm formation, HomD, a member of Hom OMP family is associated with moderate biofilm former (58.3%) to hyper biofilm former (66.7%) H. pylori strains 46 .…”

Section: Discussionmentioning

confidence: 86%

“…Purification of recombinant HomA and HomB protein was confirmed on 8% SDS PAGE gel. Heat modifiability assay was done according to the method previously reported 45 , briefly, purified HomA and HomB with either detergent (LDAO, CHAPS, TWEEN20) with respective 4× CMC concentration and 1 mM lipids (DOPC and DMPC) added samples were boiled at 95 °C for 10 min and unboiled protein samples were run on 12% PAGE with 0.5% SDS at 150 V in cooling condition.…”

Section: Methodsmentioning

confidence: 99%

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Biophysical characterization of the homodimers of HomA and HomB, outer membrane proteins of Helicobacter pylori

Tamrakar

Singh

Kumar

et al. 2021

Sci Rep

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Helicobacter pylori is a Gram-negative bacterium that causes chronic inflammations in the stomach area and is involved in ulcers, which can develop into gastric malignancies. H. pylori attaches and colonizes to the human epithelium using some of their outer membrane proteins (OMPs). HomB and HomA are the most studied OMPs from H. pylori as they play a crucial role in adherence, hyper biofilm formation, antibiotic resistance and are also associated with severe gastric malignancies. The role of HomA and HomB in pathogenesis concerning their structure and function has not been evaluated yet. In the present study, we explored the structural aspect of HomA and HomB proteins using various computational, biophysical and small-angle X-ray scattering (SAXS) techniques. Interestingly, the in-silico analysis revealed that HomA/B consists of 8 discontinuous N and C terminal β-strands forming a small β-barrel, along with a large surface-exposed globular domain. Further, biophysical experiments suggested that HomA and HomB are dimeric and most likely the cysteine residues present on surface-exposed loops participate in protein–protein interactions. Our study provides essential structural information of unexplored proteins of the Hom family that can help in a better understanding of H. pylori pathogenesis.

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Section: Discussionmentioning

confidence: 86%

Section: Methodsmentioning

confidence: 99%

Biophysical characterization of the homodimers of HomA and HomB, outer membrane proteins of Helicobacter pylori

Tamrakar

Singh

Kumar

et al. 2021

Sci Rep

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“…The structure of OafB was predicted by RaptorX ( Wang et al, 2016 ; Källberg et al, 2014 ; Ma et al, 2015 ) using the protein sequence of a Salmonella rhamnose O-acetyltransferase (OafB). This method has been successfully validated with numerous proteins ( Sharma et al, 2021 ; Mariani et al, 2011 ; Lopes-Rodrigues et al, 2019 ; Bakar and Kaplan-türköz, 2017 ; Xu and Wang, 2019 ). The structure of OafB consists of two key domains: the AT3 domain and SGNH domain ( Figure 1C ).…”

Section: Resultsmentioning

confidence: 99%

A novel fold for acyltransferase-3 (AT3) proteins provides a framework for transmembrane acyl-group transfer

Newman

Tindall

Mader

et al. 2023

eLife

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Acylation of diverse carbohydrates occurs across all domains of life and can be catalysed by proteins with a membrane bound acyltransferase-3 (AT3) domain (PF01757). In bacteria, these proteins are essential in processes including symbiosis, resistance to viruses and antimicrobials, and biosynthesis of antibiotics, yet their structure and mechanism are largely unknown. In this study, evolutionary co-variance analysis was used to build a computational model of the structure of a bacterial O-antigen modifying acetyltransferase, OafB. The resulting structure exhibited a novel fold for the AT3 domain, which molecular dynamics simulations demonstrated is stable in the membrane. The AT3 domain contains 10 transmembrane helices arranged to form a large cytoplasmic cavity lined by residues known to be essential for function. Further molecular dynamics simulations support a model where the acyl-coA donor spans the membrane through accessing a pore created by movement of an important loop capping the inner cavity, enabling OafB to present the acetyl group close to the likely catalytic resides on the extracytoplasmic surface. Limited but important interactions with the fused SGNH domain in OafB are identified, and modelling suggests this domain is mobile and can both accept acyl-groups from the AT3 and then reach beyond the membrane to reach acceptor substrates. Together this new general model of AT3 function provides a framework for the development of inhibitors that could abrogate critical functions of bacterial pathogens.

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“…The structure of OafB was predicted by RaptorX (66-68) using the protein sequence of a Salmonella rhamose O-acetyltransferase (OafB). This method has been successfully validated with numerous proteins (69)(70)(71)(72)(73). The structure of OafB consists of two key domains: the AT3 domain and SGNH domain (Fig.…”

Section: Raptorx Model Of Oafb Supports Specific Topology Predictions...mentioning

confidence: 99%

A novel fold for acyltransferase-3 (AT3) proteins provides a framework for transmembrane acyl-group transfer

Newman

Tindall

Mader

et al. 2022

Preprint

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Acylation of diverse carbohydrates occurs across all domains of life and can be catalysed by proteins with a membrane bound acyltransferase-3 (AT3) domain (PF01757). In bacteria, these proteins are essential in processes including symbiosis, resistance to viruses and antimicrobials, and biosynthesis of antibiotics, yet their structure and mechanism is largely unknown. In this study, evolutionary co-variance analysis was used to build a computational model of the structure of a bacterial O-antigen modifying acetyltransferase, OafB. The resulting structure exhibited a novel fold for the AT3 domain, which molecular dynamics simulations demonstrated is stable in the membrane. The AT3 domain contains 10 transmembrane helices arranged to form a large cytoplasmic cavity lined by residues known to be essential for function. Further molecular dynamics simulations support a model where the acyl-coA donor spans the membrane through accessing a pore created by movement of an important loop capping the inner cavity, enabling OafB to present the acetyl group close to the likely catalytic resides on the extracytoplasmic surface. Limited but important interactions with the fused SGNH domain in OafB are identified and modelling suggests this domain is mobile and can both accept acyl-groups from the AT3 and then reach beyond the membrane to reach acceptor substrates. Together this new general model of AT3 function provides a framework for the development of inhibitors that could abrogate critical functions of bacterial pathogens.

show abstract

3D structure of a Brucella melitensis porin: molecular modelling in lipid membranes

Cited by 6 publications

References 64 publications

Biophysical characterization of the homodimers of HomA and HomB, outer membrane proteins of Helicobacter pylori

Biophysical characterization of the homodimers of HomA and HomB, outer membrane proteins of Helicobacter pylori

A novel fold for acyltransferase-3 (AT3) proteins provides a framework for transmembrane acyl-group transfer

A novel fold for acyltransferase-3 (AT3) proteins provides a framework for transmembrane acyl-group transfer

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