HUBER Roland

Protein-protein interactions in paralogues: Electrostatics modulates specificity on a conserved steric scaffold

Published date : 17 Oct 2017

An improved knowledge of protein-protein interactions is essential for better understanding of metabolic and signaling networks, and cellular function. Progress tends to be based on structure determination and predictions using known structures, along with computational methods based on evolutionary information or detailed atomistic descriptions.

type
Journal Paper
journal
PLOS ONE, 10 Oct 2017, doi: 10.1371/journal.pone.018592
Impact Factor
2.806

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.

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

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.

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

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

Energetics and Dynamics Across the Bcl-2-Regulated Apoptotic Pathway Reveal Distinct Evolutionary Determinants of Specificity and Affinity

Published date : 20 Oct 2016

Critical regulatory pathways are replete with instances of intra- and interfamily protein-protein interactions due to the pervasiveness of gene duplication throughout evolution. Discerning the specificity determinants within these systems has proven a challenging task. Here, we present an energetic analysis of the specificity determinants within the Bcl-2 family of proteins (key regulators of the intrinsic apoptotic pathway) via a total of ∼20 μs of simulation of 60 distinct protein-protein complexes.

type
Journal Paper
journal
Structure, Vol 24, Issue 11, pg 2024-2033, 1 Nov 2016, doi: 10.1016/j.str.2016.09.006
Impact Factor
5.237

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.

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

Hydrocarbons are essential for optimal cell size, division and growth of cyanobacteria

Published date : 05 Oct 2016

Cyanobacteria are intricately organized, incorporating an array of internal thylakoid membranes, the site of photosynthesis, into cells no larger than other bacteria. They also synthesize C15-C19 alkanes and alkenes, which results in substantial production of hydrocarbons in the environment. All sequenced cyanobacteria encode hydrocarbon biosynthesis pathways, suggesting an important, undefined physiological role for these compounds. Here, we demonstrate that hydrocarbon-deficient mutants of Synechococcus sp. PCC 7002 and Synechocystis sp.

type
Journal Paper
journal
Plant Physiology Nov 2016, Vol. 172, No 3, Pg 1928-1940, doi:10.1104/pp.16.01205
Impact Factor
6.28

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.

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
Impact Factor
5.8

Impairing Cohesin Smc1/3 Head Engagement Compensates for the Lack of Eco1 Function

Published date : 08 Sep 2016

The cohesin ring, which is composed of the Smc1, Smc3, and Scc1 subunits, topologically embraces two sister chromatids from S phase until anaphase to ensure their precise segregation to the daughter cells. The opening of the ring is required for its loading on the chromosomes and unloading by the action of Wpl1 protein. Both loading and unloading are dependent on ATP hydrolysis by the Smc1 and Smc3 “head” domains, which engage to form two composite ATPase sites.

type
Journal Paper
journal
Structure, 2016, doi: 10.1016/j.str.2016.09.001
Impact Factor
5.237