Figure 1. Experimental and data analysis processes.

Sequential analysis of E1E2 folding and function enabled amino acids involved in each step to be identified. This screening strategy also facilitates the exclusion of mutants that are locally misfolded or that have an expression defect (Davidson and Doranz, 2014; Paes et al., 2009). Residues identified as contributing directly to MAb epitopes were excluded from the corresponding structure-function analysis using said MAbs, as they impart no structural or functional information about E1E2.