Fig. 1.

Schematic of the TBEV genome and protein C. The genome (Upper) consists of a single long ORF encoding three structural proteins (C, prM, and E) and several nonstructural proteins and two flanking noncoding sequences (not drawn to scale). Protein C (Lower) is largely α-helical (four predicted helices, HI to H IV). H I coincides approximately with a stretch of hydrophobic amino acid residues (referred to as central hydrophobic domain, chD). The engineered deletion (double-headed arrow) removes all of H I/chD and an adjacent domain in which compensating mutations restoring viability of deletion mutants were previously observed to arise (shown as shaded area). H IV is an internal signal sequence of the subsequent component of the polyprotein, protein prM. It is cleaved off from mature protein C by the action of the viral protease NS2B/3. In mutant C(▵28–89)-S the signal sequence was modified by three point mutations as indicated in the figure, creating an idealized sequence. Numbers refer to amino acid positions in protein C.