HOLDBROOK Daniel

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).

type
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

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.

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

Multiscale Molecular Dynamics Simulation Approaches to the Structure and Dynamics of Viruses

Published date : 17 Oct 2016

Viral pathogens are a significant source of human morbidity and mortality, and have a major impact on societies and economies around the world. One of the challenges inherent in targeting these pathogens with drugs is the tight integration of the viral life cycle with the host's cellular machinery. However, the reliance of the virus on the host cell replication machinery is also an opportunity for therapeutic targeting, as successful entry- and exit-inhibitors have demonstrated.

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Journal Paper
journal
Progress in Biophysics and Molecular Biology, Oct 17 2016, doi: 10.1016/j.pbiomolbio.2016.09.010
Impact Factor
2.581

South-east Asian Zika virus strain linked to cluster of cases in Singapore, August 2016

Published date : 22 Sep 2016

Zika virus (ZIKV) is an ongoing global public health emergency with 70 countries and territories reporting evidence of ZIKV transmission since 2015. On 27 August 2016, Singapore reported its first case of local ZIKV transmission and identified an ongoing cluster. Here, we report the genome sequences of ZIKV strains from two cases and find through phylogenetic analysis that these strains form an earlier branch distinct from the recent large outbreak in the Americas.

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Journal Paper
journal
Eurosurveillance, Volume 21, Issue 38, 22 September 2016, DOI: http://dx.doi.org/10.2807/1560-7917.ES.2016.21.38.30347
Impact Factor
5.8

Pushing the Envelope: Dengue Viral Membrane Coaxed into Shape by Molecular Simulations

Published date : 07 Jul 2016

Dengue virus is a flavivirus responsible for millions of infections per year. Its surface contains a phospholipid bilayer, within which are embedded the envelope (E) and membrane (M) proteins, arranged with icosahedral geometry. Exposure to low pH triggers the E proteins to undergo conformational changes, which precede fusion with the host cell membrane and release of the viral genome.

type
Journal Paper
journal
Structure 2016 Jul 6, doi: 10.1016/j.str.2016.05.014
Impact Factor
5.618

Dynamics of crowded vesicles: local and global responses to membrane composition

Published date : 16 Jun 2016

The bacterial cell envelope is composed of a mixture of different lipids and proteins, making it an inherently complex organelle. The interactions between integral membrane proteins and lipids are crucial for their respective spatial localization within bacterial cells. We have employed microsecond timescale coarse-grained molecular dynamics simulations of vesicles of varying sizes and with a range of protein and lipid compositions, and used novel approaches to measure both local and global system dynamics, the latter based on spherical harmonics analysis.

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Journal Paper
journal
PLOS One, June 16, 2016, DOI:10.1371/journal.pone.0156963
Impact Factor
3.057