HOLDBROOK Daniel

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

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
pubmed: 
28739292
Url: 
https://www.ncbi.nlm.nih.gov/pubmed/?term=28739292
Impact Factor: 
3.498
Date of acceptance: 
2017-07-20

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

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
pubmed: 
28648612
Url: 
https://www.ncbi.nlm.nih.gov/pubmed/28648612
Impact Factor: 
5.618

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

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.

type: 
Journal Paper
journal: 
Progress in Biophysics and Molecular Biology, Oct 17 2016, doi: 10.1016/j.pbiomolbio.2016.09.010
pubmed: 
27765545
Url: 
https://www.ncbi.nlm.nih.gov/pubmed/27765545
Impact Factor: 
2.581
Date of acceptance: 
2016-09-27

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

type: 
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
Url: 
http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=22588
Impact Factor: 
5.8
Date of acceptance: 
2016-09-22

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

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
pubmed: 
27396828
Url: 
http://www.ncbi.nlm.nih.gov/pubmed/27396828
Impact Factor: 
5.618
Date of acceptance: 
2016-05-11

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

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.

type: 
Journal Paper
journal: 
PLOS One, June 16, 2016, DOI:10.1371/journal.pone.0156963
Url: 
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0156963
Impact Factor: 
3.057
Date of acceptance: 
2016-06-24
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