Structure-based virtual screening toward the discovery of novel inhibitors for impeding the protein-protein interaction between HIV-1 integrase and human lens epithelium-derived growth factor (LEDGF/p75)

2017 ◽  
Vol 36 (12) ◽  
pp. 3199-3217 ◽  
Author(s):  
Umesh Panwar ◽  
Sanjeev Kumar Singh
Keyword(s):  
Growth Factor ◽  
Virtual Screening ◽  
Protein Interaction ◽  
Lens Epithelium ◽  
Human Lens ◽  
Protein Protein Interaction ◽  
Human Lens Epithelium ◽  
Hiv 1

scholarly journals Structural basis for activation of trimeric Gi proteins by multiple growth factor receptors via GIV/Girdin

2014 ◽  
Vol 25 (22) ◽  
pp. 3654-3671 ◽  
Author(s):  
Changsheng Lin ◽  
Jason Ear ◽  
Krishna Midde ◽  
Inmaculada Lopez-Sanchez ◽  
Nicolas Aznar ◽  
...  
Keyword(s):  
Growth Factor ◽  
G Proteins ◽  
Protein Interaction ◽  
Cross Talk ◽  
Tyrosine Kinases ◽  
Molecular Mechanisms ◽  
Growth Factor Receptors ◽  
Structural Basis ◽  
Nucleotide Exchange ◽  
Protein Protein Interaction

A long-standing issue in the field of signal transduction is to understand the cross-talk between receptor tyrosine kinases (RTKs) and heterotrimeric G proteins, two major and distinct signaling hubs that control eukaryotic cell behavior. Although stimulation of many RTKs leads to activation of trimeric G proteins, the molecular mechanisms behind this phenomenon remain elusive. We discovered a unifying mechanism that allows GIV/Girdin, a bona fide metastasis-related protein and a guanine-nucleotide exchange factor (GEF) for Gαi, to serve as a direct platform for multiple RTKs to activate Gαi proteins. Using a combination of homology modeling, protein–protein interaction, and kinase assays, we demonstrate that a stretch of ∼110 amino acids within GIV C-terminus displays structural plasticity that allows folding into a SH2-like domain in the presence of phosphotyrosine ligands. Using protein–protein interaction assays, we demonstrated that both SH2 and GEF domains of GIV are required for the formation of a ligand-activated ternary complex between GIV, Gαi, and growth factor receptors and for activation of Gαi after growth factor stimulation. Expression of a SH2-deficient GIV mutant (Arg 1745→Leu) that cannot bind RTKs impaired all previously demonstrated functions of GIV—Akt enhancement, actin remodeling, and cell migration. The mechanistic and structural insights gained here shed light on the long-standing questions surrounding RTK/G protein cross-talk, set a novel paradigm, and characterize a unique pharmacological target for uncoupling GIV-dependent signaling downstream of multiple oncogenic RTKs.

scholarly journals Somatic Variants in the Human Lens Epithelium: A Preliminary Assessment

2016 ◽  
Vol 57 (10) ◽  
pp. 4063 ◽  
Author(s):  
Rosana Mesa ◽  
Manoj Tyagi ◽  
George Harocopos ◽  
David Vollman ◽  
Steven Bassnett
Keyword(s):  
Lens Epithelium ◽  
Human Lens ◽  
Preliminary Assessment ◽  
Human Lens Epithelium

scholarly journals Lens epithelium-derived growth factor fusion proteins redirect HIV-1 DNA integration

2010 ◽  
Vol 107 (7) ◽  
pp. 3135-3140 ◽  
Author(s):  
A. L. Ferris ◽  
X. Wu ◽  
C. M. Hughes ◽  
C. Stewart ◽  
S. J. Smith ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fusion Proteins ◽  
Lens Epithelium ◽  
Dna Integration ◽  
Hiv 1

An Immunoperoxidase Study of Human Lens Epithelium

1990 ◽  
Vol 2 (1) ◽  
pp. 71-73 ◽  
Author(s):  
Margaret J. Jeffrey ◽  
W.T. Green ◽  
D.L. Boase ◽  
M.N. Jeffrey
Keyword(s):  
Lens Epithelium ◽  
Human Lens ◽  
Human Lens Epithelium

Extracting Biological Significant Subnetworks from Protein-Protein Interactions Induced by Differentially Expressed Genes of HIV-1 Vpr Variants

2015 ◽  
Vol 4 (4) ◽  
pp. 35-51 ◽  
Author(s):  
Bandana Barman ◽  
Anirban Mukhopadhyay
Keyword(s):  
Differentially Expressed Genes ◽  
Protein Interaction ◽  
Protein Interactions ◽  
Protein Interaction Network ◽  
Interaction Network ◽  
Differentially Expressed ◽  
Wild Type ◽  
Protein Protein Interaction ◽  
Ppi Networks ◽  
Hiv 1

Identification of protein interaction network is very important to find the cell signaling pathway for a particular disease. The authors have found the differentially expressed genes between two sample groups of HIV-1. Samples are wild type HIV-1 Vpr and HIV-1 mutant Vpr. They did statistical t-test and found false discovery rate (FDR) to identify the genes increased in expression (up-regulated) or decreased in expression (down-regulated). In the test, the authors have computed q-values of test to identify minimum FDR which occurs. As a result they found 172 differentially expressed genes between their sample wild type HIV-1 Vpr and HIV-1 mutant Vpr, R80A. They found 68 up-regulated genes and 104 down-regulated genes. From the 172 differentially expressed genes the authors found protein-protein interaction network with string-db and then clustered (subnetworks) the PPI networks with cytoscape3.0. Lastly, the authors studied significance of subnetworks with performing gene ontology and also studied the KEGG pathway of those subnetworks.

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