Structural basis for VLDLR recognition by eastern equine encephalitis virus

Pan Yang, Wanyu Li, Xiaoyi Fan, Junhua Pan, Colin J. Mann, Haley Varnum, Lars E. Clark, Sarah A. Clark, Adrian Coscia, Himanish Basu, Katherine Nabel Smith, Vesna Brusic and Jonathan Abraham ()
Additional contact information
Pan Yang: Harvard Medical School
Wanyu Li: Harvard Medical School
Xiaoyi Fan: Harvard Medical School
Junhua Pan: Harvard Medical School
Colin J. Mann: Harvard Medical School
Haley Varnum: Harvard Medical School
Lars E. Clark: Harvard Medical School
Sarah A. Clark: Harvard Medical School
Adrian Coscia: Harvard Medical School
Himanish Basu: Harvard Medical School
Katherine Nabel Smith: Harvard Medical School
Vesna Brusic: Harvard Medical School
Jonathan Abraham: Harvard Medical School

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: 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.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-50887-9 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50887-9

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-50887-9

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().