Identification of Entry Factors Involved in Hepatitis C Virus Infection Based on Host-Mimicking Short Linear Motifs
Fig 4
The AVP/SLiM-protein complex map.
Top panel: (left column) a list of AVPs with their AVPdb identification numbers that have an amino acid sequence containing one or more HCV E1/E2 SLiMs (indicated by the triangles and named at the bottom of the panel) that can bind to a subunit of a protein complex belonging to one of the six main complex groups. The relative efficacies of these AVPs in inhibiting HCV entry according to data provided in the AVPdb [56] are indicated by the circles column in the panel with the shading score shown to the right of the panel. Middle panel: the network connecting the nine SLiMs to their group A-F complex target(s). Within each group are VIPs of all the complexes: ovals represent VIPsdirect (gray ovals are R6 VIPsdirect), and rectangles represent VIPsindirect (not all VIPsindirect are shown). The ovals and rectangles in bold outline are known HCV entry factors. The horizontal bar represents the plasma membrane, the VIPs below the bar and within the shaded area are ‘peripheral membrane proteins’, and those spanning the bar are ‘integral membrane proteins’. APOE is a peripheral membrane protein located at the extracellular side of the cell membrane. A connection between a viral SLiM and a complex group indicates that at least one protein in the group is targeted by HCV E1 and/or E2 via the viral SLiM. The thickness of the connection roughly scales to the number of proteins targeted by the SLiM in the group. The three numbers in the parenthesis are the number of VIPsdirect, total VIPs (i.e., VIPsdirect plus VIPsindirect), and unique subunits in the complex group. Bottom panel: the KEGG pathways enriched in the complex group (Benjamini-Hochberg adjusted P < 0.001) (see S6 Table for the pathway names). The gray scale at bottom right indicate the significance of the P-values. The functions of the individual KEGG pathways are shown at the left of the panel and the main functionality at the right of the panel.