Structural highlights
Function
LRAD3_MOUSE May influence APP processing, resulting in a decrease in sAPP-alpha production and increased amyloidogenic P3 peptide production (PubMed:21795536). May regulate ITCH and NEDD4 E3 ligase activity and degradation (By similarity).[UniProtKB:Q86YD5][1]
Publication Abstract from PubMed
LDLRAD3 is a recently defined attachment and entry receptor for Venezuelan equine encephalitis virus (VEEV)(1), a New World alphavirus that causes severe neurological disease in humans. Here we present near-atomic-resolution cryo-electron microscopy reconstructions of VEEV virus-like particles alone and in a complex with the ectodomains of LDLRAD3. Domain 1 of LDLRAD3 is a low-density lipoprotein receptor type-A module that binds to VEEV by wedging into a cleft created by two adjacent E2-E1 heterodimers in one trimeric spike, and engages domains A and B of E2 and the fusion loop in E1. Atomic modelling of this interface is supported by mutagenesis and anti-VEEV antibody binding competition assays. Notably, VEEV engages LDLRAD3 in a manner that is similar to the way that arthritogenic alphaviruses bind to the structurally unrelated MXRA8 receptor, but with a much smaller interface. These studies further elucidate the structural basis of alphavirus-receptor interactions, which could inform the development of therapies to mitigate infection and disease against multiple members of this family.
Structure of Venezuelan equine encephalitis virus in complex with the LDLRAD3 receptor.,Basore K, Ma H, Kafai NM, Mackin S, Kim AS, Nelson CA, Diamond MS, Fremont DH Nature. 2021 Oct;598(7882):672-676. doi: 10.1038/s41586-021-03963-9. Epub 2021 , Oct 13. PMID:34646020[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ranganathan S, Noyes NC, Migliorini M, Winkles JA, Battey FD, Hyman BT, Smith E, Yepes M, Mikhailenko I, Strickland DK. LRAD3, a novel low-density lipoprotein receptor family member that modulates amyloid precursor protein trafficking. J Neurosci. 2011 Jul 27;31(30):10836-46. PMID:21795536 doi:10.1523/JNEUROSCI.5065-10.2011
- ↑ Basore K, Ma H, Kafai NM, Mackin S, Kim AS, Nelson CA, Diamond MS, Fremont DH. Structure of Venezuelan equine encephalitis virus in complex with the LDLRAD3 receptor. Nature. 2021 Oct;598(7882):672-676. PMID:34646020 doi:10.1038/s41586-021-03963-9
