Natural genetic engineering of hepatitis C virus NS5A for immune system counterattack.
The Hepatitis C virus nonstructural 5A (NS5A) protein is a hydrophilic phosphoprotein with diverse functions. The domain assignment of NS5A had been refined using a systematic in silico bioinformatics approach using DOMAC, the protein is divided into three domains and domain III is subdivided into two subdomains using ProDom and SSEP servers. The fold structure for domains II and III were predicted using the meta-server 3D-Jury. Scanning motif databases (SMART, BLOCKS, and PROSITE) gave new motifs. Two important motifs, the interleukins 1 and 8 interaction motifs, relating to NS5A function in inducing the interleukin 8 promoter, were discovered from the BLOCKS scan. Protein-protein interaction motifs were predicted as hot loops and disordered regions, corresponding to binding regions with the ds-protein kinase R, viral polymerase, and Src homology 3 signaling proteins binding motif. Other hot loops were predicted in the V3 region and in the single-stranded DNA-binding protein motif. The different mechanisms by which the NS5A protein leads to immune system signaling dysfunction points to the natural genetic engineering of this protein.
El Hefnawi
Mahmoud M
MM
Informatics and Systems Department, Division of Engineering Research Sciences, the National Research Centre, Egypt. mahef@aucegypt.edu
El Behaidy
Wessam H
WH
Youssif
Aliaa A
AA
Ghalwash
Atek Z
AZ
El Housseiny
Lamya A
LA
Zada
Suher
S
D000595:Amino Acid Sequence; D016174:Hepacivirus / Q000235:genetics* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D015398:Signal Transduction / Q000276:immunology*; D017361:Viral Nonstructural Proteins / Q000235:genetics* / Q000378:metabolism; D014779:Virus Replication; D012324:RNA-Dependent RNA Polymerase
D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase