HUBER Roland

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

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.

type: 
Journal Paper
journal: 
Bulletin of the World Health Organization, 2017, Jul 1: 95(7): Pg 517-525i
Url: 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5487971/
Impact Factor: 
4.939
Date of acceptance: 
2017-01-19

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

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

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
pubmed: 
28362432
Url: 
http://www.pnas.org/content/early/2017/05/03/1619609114.abstract
Impact Factor: 
9.661
Date of acceptance: 
2017-05-12

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

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

type: 
Journal Paper
journal: 
JCI Insight. 2017 Apr 20;2(8). pii: 92428. doi: 10.1172/jci.insight.92428
Url: 
https://insight.jci.org/articles/view/92428
Date of acceptance: 
2017-04-21

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

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
pubmed: 
27773689
Url: 
https://www.ncbi.nlm.nih.gov/pubmed/27773689
Impact Factor: 
5.237
Date of acceptance: 
2016-09-28

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

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

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
pubmed: 
27707888
Url: 
http://www.plantphysiol.org/content/172/3/1928.long
Impact Factor: 
6.28
Date of acceptance: 
2016-10-05

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

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

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
pubmed: 
27692962
Url: 
http://www.cell.com/structure/abstract/S0969-2126(16)30265-9
Impact Factor: 
5.237
Date of acceptance: 
2016-08-05

A Reversible Association between Smc Coiled Coils is Regulated by Lysine acetylation and Is Required for Cohesin Association with the DNA

Cohesin is a ring-shaped protein complex that is capable of embracing DNA. Most of the ring circumference is comprised of the anti-parallel intramolecular coiled coils of the Smc1 and Smc3 proteins, which connect globular head and hinge domains. Smc coiled coil arms contain multiple acetylated and ubiquitylated lysines. To investigate the role of these modifications, we substituted lysines for arginines to mimic the unmodified state and uncovered genetic interaction between the Smc arms.

type: 
Journal Paper
journal: 
Molecular Cell, Volume 63, Issue 6, p1044–1054, 15 September 2016, doi: 10.1016/j.molcel.2016.08.008
pubmed: 
27618487
Url: 
https://www.ncbi.nlm.nih.gov/pubmed/27618487
Impact Factor: 
13.958
Date of acceptance: 
2016-08-05
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