Multiscale Simulation, Modelling, and Design in Biological Chemistry and Biophysics

A polar SxxS motif drives assembly of the transmembrane domains of Toll-like receptor 4

Published date : 22 Jul 2017

Like all members of the Toll-like receptor (TLR) family, TLR4 comprises of a large ectodomain (ECD) involved in ligand recognition at the cell-surface, and a cytosolic Toll/interleukin-1 receptor (TIR) signalling domain, linked by a lipid membrane-anchored transmembrane (TM) domain (TMD).

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Journal Paper
journal
Biochimica et Biophysica Acta (BBA) - Biomembranes, 2017 Jul 22;1859(10):2086-2095. doi: 10.1016/j.bbamem.2017.07.010
Impact Factor
3.498

Systematic analysis of protein identity between Zika virus and other arthropod-borne viruses

Published date : 18 Jul 2017

Objective To analyse the proportions of protein identity between Zika virus and dengue, Japanese encephalitis, yellow fever, West Nile and chikungunya viruses as well as polymorphism between different Zika virus strains.

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Journal Paper
journal
Bulletin of the World Health Organization, 2017, Jul 1: 95(7): Pg 517-525i
Impact Factor
4.939

A Spring-Loaded Mechanism Governs the Clamp-like Dynamics of the Skp Chaperone

Published date : 22 Jun 2017

The trimeric periplasmic holdase chaperone Skp binds and stabilizes unfolded outer membrane proteins (OMPs) as part of bacterial OMP biogenesis. Skp binds client proteins in its central cavity, thereby reducing its backbone dynamics, but the molecular mechanisms that govern Skp dynamics and adaptation to differently sized clients remains unknown.

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Journal Paper
journal
Structure, 2017 Jul 5;25(7):1079-1088.e3. doi: 10.1016/j.str.2017.05.018
Impact Factor
5.618

Aggregation of thrombin-derived C-terminal fragments as a previously undisclosed host defense mechanism

Published date : 04 May 2017

Effective control of endotoxins and bacteria is crucial for normal wound healing. During injury, the key enzyme thrombin is formed, leading to generation of fibrin. Here, we show that human neutrophil elastase cleaves thrombin, generating 11-kDa thrombin-derived C-terminal peptides (TCPs), which bind to and form amorphous amyloid-like aggregates with both bacterial lipopolysaccharide (LPS) and gram-negative bacteria.

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Journal Paper
journal
Proceedings of the National Academy of Sciences (PNAS), May 4, 2017, doi: 10.1073/pnas.1619609114
Impact Factor
9.661

Progress in Molecular Dynamics Simulations of Bacterial Cell Envelopes

Published date : 03 May 2017

Bacteria are protected by complex molecular architectures known as the cell envelope. The cell envelope is composed of regions with distinct chemical compositions and physical properties, namely, membranes and a cell wall. To develop novel antibiotics to combat pathogenic bacteria, molecular level knowledge of the structure, dynamics, and interplay between the chemical components of the cell envelope that surrounds bacterial cells is imperative.

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Journal Paper
journal
The Journal of Physical Chemistry Letters, 2017 Jun 1;8(11):2513-2518. doi: 10.1021/acs.jpclett.7b00473
Impact Factor
9.353

Full-length, Oligomeric Structure of Wzz Determined by Cryoelectron Microscopy Reveals Insights into Membrane-Bound States

Published date : 20 Apr 2017

Wzz is an integral inner membrane protein involved in regulating the length of lipopolysaccharide O-antigen glycans and essential for the virulence of many Gram-negative pathogens. In all Wzz homologs, the large periplasmic domain is proposed to be anchored by two transmembrane helices, but no information is available for the transmembrane and cytosolic domains. Here we have studied purified oligomeric Wzz complexes using cryoelectron microscopy and resolved the transmembrane regions within a semi-continuous detergent micelle.

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Journal Paper
journal
Structure, 2017 May 2;25(5):806-815. e3. doi: 10.1016/j.str.2017.03.017
Impact Factor
5.618

Cross-reactive dengue human monoclonal antibody prevents severe pathologies and death from Zika virus infections

Published date : 20 Apr 2017

Zika virus (ZIKV) infections have been linked with neurological complications and congenital Zika syndrome. Given the high level of homology between ZIKV and the related flavivirus dengue virus (DENV), we investigated the level of cross-reactivity with ZIKV using a panel of DENV human mAbs. A majority of the mAbs showed binding to ZIKV virions, with several exhibiting neutralizing capacities against ZIKV in vitro. Three of the best ZIKV-neutralizing mAbs were found to recognize diverse epitopes on the envelope (E) glycoprotein: the highly conserved fusion-loop peptide, a

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Journal Paper
journal
JCI Insight. 2017 Apr 20;2(8). pii: 92428. doi: 10.1172/jci.insight.92428

Polar N-terminal Residues Conserved in Type 2 Secretion Pseudopilins Determine Subunit Targeting and Membrane Extraction Steps during Fibre Assembly

Published date : 17 Apr 2017

Bacterial type 2 secretion systems (T2SS), type 4 pili, and archaeal flagella assemble fibres from initially membrane-embedded pseudopilin and pilin subunits. Fibre subunits are made as precursors with positively charged N-terminal anchors, whose cleavage via the prepilin peptidase, essential for pilin membrane extraction and assembly, is followed by N-methylation of the mature (pseudo)pilin N terminus. The conserved Glu residue at position 5 (E5) of mature (pseudo)pilins is essential for assembly.

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Journal Paper
journal
Journal of Molecular Biology, Vol. 429, Issue 11, 2 Jun 2017, Pg 1746-1765
Impact Factor
4.333

OmpA: A Flexible Clamp for Bacterial Cell Wall Attachment

Published date : 17 Nov 2016

The envelope of Gram-negative bacteria is highly complex, containing separate outer and inner membranes and an intervening periplasmic space encompassing a peptidoglycan (PGN) cell wall. The PGN scaffold is anchored non-covalently to the outer membrane via globular OmpA-like domains of various proteins. We report atomically detailed simulations of PGN bound to OmpA in three different states, including the isolated C-terminal domain (CTD), the full-length monomer, or the complete full-length dimeric form.

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Journal Paper
journal
Structure 2016, Vol. 24, Issue 12, 6 Dec 2016, Pg 2227-2235, doi: 10.1016/j.str.2016.10.009
Impact Factor
5.237