Extended Data Fig. 2. Sequence alignment of E2 proteins of the VEEV complex and other alphaviruses.

Amino acid sequence alignment of E2 proteins of various VEEV strains (IAB strain TC-83, AAB02517; IAB strain TrD, AAC19322; IC strain INH9813, AJP13627; ID strain ZPC738, AUV65225) and other alphaviruses (EEEV strain FL93-939, ABL84687; WEEV strain CBA87, ABD98014; SINV strain Girdwood, AUV65223; CHIKV strain 37997, ABX40011). Structure-based sequence alignments were performed between alphaviruses that do (group 1, left margin) or do not (groups 2 and 3, left margin) use LDLRAD3 as a receptor for infection using PROMALS3D with VEEV numbering. The figure was prepared using ESPript 3.0. Domains are coloured (A (light cyan), B (medium cyan), C (blue) and β linker (medium cyan)) and indicated above the sequence, along with the secondary structure features and nomenclature (PDB: 3J0C; ref. ²¹). Red boxes indicate residues that are 100% conserved; white boxes and red letters indicate homologous residues within the specific group; white boxes and black letters indicate non-conserved residues. Determinants of receptor binding to the individual E2–E1 heterodimers are indicated by stars below the alignment and are coloured magenta if specific to LDLRAD3, cyan if specific to MXRA8, or yellow if shared between the two receptors. Wrapped denotes contacts to the wrapped E2–E1 heterodimer, the fusion loop of which is covered by LDLRAD3(D1) or MXRA8. Intraspike refers to the intraspike heterodimer, which is adjacent to the wrapped heterodimer but within the same trimeric spike. Contact residues were determined using PDBePISA.