An Integrative In Silico Model of Hepatitis C Virus Non-structural 5a Protein

A model for the non-structural 5a (NS5A) protein of Hepatitis-C virus is proposed. It is a hub promiscuous multifunctional protein with roles in virus replication and host interactions. The 3D-structure for domainII was predicted based on, the Homo Sapiens Replication factor-A protein-1 (RPA1), as a template using consensus meta-servers results. DomainIII is an intrinsically unstructured domain (61% intrinsically-disorder regions) that lacks a unique 3Dstructure and participates in diverse protein interactions in different situations. It also has a single-stranded DNAbinding protein motif (SSDP) signature for pyrimidine binding during viral replication. Two protein binding motifs with high sequence conservation and disordered regions are proposed; the first corresponds to an Interleukin-8B receptor signature (IL-8R-B), while the second has a lymphotoxin beta receptor (LTβR) high local similarity. A mechanism is proposed to their contribution to NS5A Interferon signaling pathway interception. Lastly, the overlapping between LTβR and SSDP is considered as a sign for NS5A date hubs.

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