8UA8

Structure of Semliki Forest virus VLP in complex with VLDLR LA2

Summary for 8UA8

• Entry DOI: 10.2210/pdb8ua8/pdb
• EMDB information: 42054
• Descriptor: Glycoprotein E1, Glycoprotein E2, Assembly protein E3, ... (9 entities in total)
• Functional Keywords: semliki forest virus, receptor, virus like particle
• Biological source: Semliki Forest virus; More
• Total number of polymer chains: 17
• Total formula weight: 476837.58

Authors

Abraham, J.,Yang, P.,Li, W.,Fan, X.,Pan, J. (deposition date: 2023-09-20, release date: 2024-08-14, Last modification date: 2025-05-28)

Primary citation

Yang, P.,Li, W.,Fan, X.,Pan, J.,Mann, C.J.,Varnum, H.,Clark, L.E.,Clark, S.A.,Coscia, A.,Basu, H.,Smith, K.N.,Brusic, V.,Abraham, J.
Structural basis for VLDLR recognition by eastern equine encephalitis virus.
Nat Commun, 15:6548-6548, 2024

PubMed Abstract: Eastern equine encephalitis virus (EEEV) is the most virulent alphavirus that infects humans, and many survivors develop neurological sequelae, including paralysis and intellectual disability. Alphavirus spike proteins comprise trimers of heterodimers of glycoproteins E2 and E1 that mediate binding to cellular receptors and fusion of virus and host cell membranes during entry. We recently identified very-low density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2) as cellular receptors for EEEV and a distantly related alphavirus, Semliki Forest virus (SFV). Here, we use single-particle cryo-electron microscopy (cryo-EM) to determine structures of the EEEV and SFV spike glycoproteins bound to the VLDLR ligand-binding domain and found that EEEV and SFV interact with the same cellular receptor through divergent binding modes. Our studies suggest that the ability of LDLR-related proteins to interact with viral spike proteins through very small footprints with flexible binding modes results in a low evolutionary barrier to the acquisition of LDLR-related proteins as cellular receptors for diverse sets of viruses.

PubMed: 39095394
DOI: 10.1038/s41467-024-50887-9

Experimental method

ELECTRON MICROSCOPY (3.7 Å)