The role of Antibody Vκ Framework 3 region towards Antigen binding: Effects on recombinant production and Protein L binding

Antibody research has traditionally focused on heavy chains, often neglecting the important complementary role of light chains in antibody formation and secretion. In the light chain, the complementarity-determining region 3 (VL-CDR3) is specifically implicated in disease states. By modulating VL-CDR3 exposure on the scaffold through deletions in the framework region 3 (VL-FWR3), we further investigated the effects on secretion in recombinant production and antigen binding kinetics.

type: 
Journal Paper
journal: 
Scientific Reports 7, Article no: 3766 (2017), doi:10.1038/s41598-017-02756-3
Url: 
https://www.nature.com/articles/s41598-017-02756-3
Impact Factor: 
5.228
Date of acceptance: 
2017-04-18

The interfacial character of antibody paratopes: analysis of antibody-antigen structures

In this study, computational methods are applied to investigate the general properties of antigen engaging residues of a paratope from a non-redundant dataset of 403 antibody-antigen complexes to dissect the contribution of hydrogen bonds, hydrophobic, van der Waals contacts and ionic interactions, as well as role of water molecules in the antigen-antibody interface. Consistent with previous reports using smaller datasets, we found that Tyr, Trp, Ser, Asn, Asp, Thr, Arg, Gly, His contribute substantially to the interactions between antibody and antigen.

type: 
Journal Paper
journal: 
Bioinformatics, 2017, doi: 10.1093/bioinformatics/btx389
Url: 
https://academic.oup.com/bioinformatics/article-lookup/doi/10.1093/bioinformatics/btx389
Impact Factor: 
7.307
Date of acceptance: 
2017-06-11

Targeting YAP/TAZ-TEAD protein-protein interactions using fragment-based and computational modeling approaches

The Hippo signaling pathway, which is implicated in the regulation of organ size, has emerged as a potential target for the development of cancer therapeutics. YAP, TAZ (transcription co-activators) and TEAD (transcription factor) are the downstream transcriptional machinery and effectors of the pathway. Formation of the YAP/TAZ-TEAD complex leads to transcription of growth-promoting genes. Conversely, disrupting the interactions of the complex decreases cell proliferation. Herein, we screened a 1000-member fragment library using Thermal Shift Assay and identified a hit fragment.

type: 
Journal Paper
journal: 
PLoS One, 2017 Jun 1, doi: org/10.1371/journal.pone.0178381
Url: 
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0178381
Impact Factor: 
3.1
Date of acceptance: 
2017-05-11

Systems-based approach to examine the cytokine responses in primary mouse lung macrophages infected with low pathogenic avian Influenza virus circulating in South East Asia

BACKGROUND:
Influenza A virus (IAV) is a major public health concern, being responsible for the death of approximately half a million people each year. Zoonotic transmissions of the virus from swine and avian origin have occurred in the past, and can potentially lead to the emgergence of new IAV stains in future pandemics. Pulmonary macrophages have been implicated in disease severity in the lower airway, and understanding the host response of macrophages infected with avian influenza viruses should provide new therapeutic strategies.

RESULTS:

type: 
Journal Paper
journal: 
BMC Genomics. 2017 May 30;18(1):420. doi: 10.1186/s12864-017-3803-6
pubmed: 
28558796
Url: 
https://bmcgenomics.biomedcentral.com/articles/10.1186/s12864-017-3803-6
Impact Factor: 
3.867
Date of acceptance: 
2017-05-05

Designing dual inhibitors of Mdm2/MdmX: Unexpected coupling of water with gatekeeper Y100/99

Mdm2 and MdmX share high structural similarity in their N-terminal domains, yet dual inhibitors are challenging to design due to differences in the conformations of the binding pockets, and notably of the proposed gatekeeper residue, Y100/99. Analysis of crystal structures and molecular dynamics (MD) simulations of complexes of Mdm2 and MdmX resulted in the identification of a water molecule with a long residence time that appears to be modulated by the conformation of Y100/99.

type: 
Journal Paper
Url: 
http://onlinelibrary.wiley.com/doi/10.1002/prot.25310/abstract
Impact Factor: 
2.499
Date of acceptance: 
2017-04-17

Hydration effects on the efficacy of the Epidermal growth factor receptor kinase inhibitor afatinib

Small molecules targeting the EGFR tyrosine kinase domain have been used with some success at treating patients with non-small cell lung cancer driven by activating mutations in the kinase domain. The initial class of inhibitors displaced ATP noncovalently but were rendered ineffective due to the development of resistance mutations in the kinase domain. These were overcome by the development of covalent inhibitors such as afatinib which also bind in the ATP pocket.

type: 
Journal Paper
journal: 
Scientific Reports 7, Article no: 1540 (2017), doi:10.1038/s41598-017-01491-z
Url: 
https://www.nature.com/articles/s41598-017-01491-z?WT.feed_name=subjects_biophysics
Impact Factor: 
5.228
Date of acceptance: 
2017-03-28

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
Url: 
http://www.pnas.org/content/early/2017/05/03/1619609114.abstract
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

Regulation of Transcriptional Activators by DNA-Binding Domain Ubiquitination

Ubiquitin is a key component of the regulatory network that maintains gene expression in eukaryotes, yet the molecular mechanism(s) by which non-degradative ubiquitination modulates transcriptional activator (TA) function is unknown. Here endogenous p53, a stress-activated transcription factor required to maintain health, is stably monoubiquitinated, following pathway activation by IR or Nutlin-3 and localized to the nucleus where it becomes tightly associated with chromatin.

type: 
Journal Paper
journal: 
Cell Death and Differentiation 2017 May;24(5):903-916. doi: 10.1038/cdd.2017.42
pubmed: 
, PMID: 28362432
Url: 
https://www.ncbi.nlm.nih.gov/pubmed/28362432
Impact Factor: 
8.218
Date of acceptance: 
2017-02-16

A novel toolbox to investigate tissue spatial organization applied to the study of the islets of Langerhans

Thanks to the development of new 3D Imaging techniques, volumetric data of thick samples, especially tissues, are commonly available. Several algorithms were proposed to analyze cells or nuclei in tissues, however these tools are limited to two dimensions. Within any given tissue, cells are not likely to be organized randomly and as such have specific patterns of cell-cell interaction forming complex communication networks. In this paper, we propose a new set of tools as an approach to segment and analyze tissues in 3D with single cell resolution.

type: 
Journal Paper
journal: 
Scientific Reports 7, Article number: 44261 (2017), doi:10.1038/srep44261
Url: 
http://www.nature.com/articles/srep44261
Impact Factor: 
5.228
Date of acceptance: 
2017-02-07
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