Fig. 2. Atomic model of LDLRAD3 interactions with VEEV.

a, Structure-based sequence alignment with the labelled secondary structure of various LA domains, including mouse (m) LDLRAD3 domains 1–3, human (h) LDLR CR2 and CR3 (PDB: 5OYL and 5OY9, respectively³¹), and human VLDLR-V3 (PDB: 3DPR; ref. ³³). Contact residues of LDLRAD3(D1) to the wrapped and intraspike VEEV E2–E1 heterodimers are shaded dark and/or light purple, respectively. Contact residues of the cysteine-rich domain 2 of LDLR (LDLR-CR2) and LDLR-CR3 to glycoprotein G of VSV (VSV G) are shaded green and contact residues of VLDL receptor module 3 (VLDLR-V3) to viral protein 1 (VP1) of human rhinovirus 2 (HRV2) are shaded pink, as determined by PDBePISA (www.ebi.ac.uk/pdbe/pisa/) (Fig. 4c–e). The brackets and rectangles indicate residues that form disulfide bonds and coordinate calcium, respectively. The figure was prepared using ALINE³³. b, Ribbon diagram of LDLRAD3(D1) and surface representation of its wrapped and intraspike E2–E1 heterodimers. LDLRAD3(D1) and VEEV E2–E1 are coloured by domain. LDLRAD3(D1) (purple); chain E1: DI (light grey), DII (medium grey), DIII (dark grey) and fusion loop (FL) (orange); chain E2: A domain (cyan), β-linker (medium blue), B domain (dark cyan) and C domain (blue). The disulfide bonds and calcium ion in the ribbon diagram are coloured yellow and green, respectively. c, d, Paired isolated views of electron density and a model of LDLRAD3(D1) and its wrapped (c) or intraspike (d) heterodimers. Wrapped refers to the E2–E1 heterodimer, the fusion loop of which is covered by LDLRAD3. Intraspike refers to the heterodimer adjacent to the wrapped heterodimer but within the same trimeric spike. The naming convention is consistent with previous alphavirus–receptor structural studies²³. The arrows indicate the regions that are magnified in the insets, which contain views of LDLRAD3(D1). Proteins are coloured by domain as described in b. N-linked glycans are shown as balls and sticks and coloured by heteroatom. The disulfide bonds and calcium ion are coloured yellow and green, respectively.