Conformational changes in Chikungunya virus E2 protein upon heparan sulfate receptor binding explain mechanism of E2-E1 dissociation during viral entry.

Conformational changes in Chikungunya virus E2 protein upon heparan sulfate receptor binding explain mechanism of E2-E1 dissociation during viral entry.
Biosci Rep. 2019 Jun 05;:
Authors: Sahoo B, Chowdary TK
Abstract
Receptor-binding is the first step in viral cell entry. In enveloped virus cell entry, viral and host membrane fusion follows receptor-binding. Viral surface receptor-binding protein associates with membrane fusion protein and masks its structure, to prevent pre-mature fusion activity. Dissociation of receptor-binding protein from fusion protein is an essential step before membrane fusion. Mechanism of receptor-binding leading to dissociation of receptor-binding and fusion protein is poorly understood in alphaviruses. Chikungunya virus (CHIKV), an alphavirus, re-emerged as a global pathogen in recent past. CHIKV surface envelope proteins, E2 and E1, function as receptor-binding and fusion protein, respectively. Site of heparan sulfate (HS) receptor binding on E2-E1 heterodimer and its effect on E2-E1 heterodimer conformation is not known. Using molecular docking, we mapped HS binding to a positively-charged pocket on E2, that is structurally conserved in alphaviruses. Based on our results from docking and sequence analysis, we identified a novel HS binding sequence motif in E2. Purified E2 binds to heparin and HS specifically through charge interactions. Binding affinity of E2 to HS is comparable to other known HS-prot...

Source: Bioscience Reports - June 4, 2019 Category: Biomedical Science Authors: Sahoo B, Chowdary TK Tags: Biosci Rep Source Type: research