7jz4

Crystal structure of broadly Plasmodium RIFIN reactive LAIR1-inserted antibody MGD21Crystal structure of broadly Plasmodium RIFIN reactive LAIR1-inserted antibody MGD21

Structural highlights

7jz4 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.747Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

RIFIN, a large family of Plasmodium variant surface antigens, plays a crucial role in malaria pathogenesis by mediating immune suppression through activation of inhibitory receptors such as LAIR1, and antibodies with LAIR1 inserts have been identified that bind infected erythrocytes through RIFIN. However, details of RIFIN-mediated LAIR1 recognition and receptor activation have been unclear. Here, we use negative-stain EM to define the architecture of LAIR1-inserted antibodies and determine crystal structures of RIFIN-variable 2 (V2) domain in complex with a LAIR1 domain. These structures reveal the LAIR1-binding region of RIFIN to be hydrophobic and membrane-distal, to exhibit extensive structural diversity, and to interact with RIFIN-V2 in a one-to-one fashion. Through structural and sequence analysis of various LAIR1 constructs, we identify essential elements of RIFIN-binding on LAIR1. Furthermore, a structure-derived LAIR1-binding sequence signature ascertained >20 LAIR1-binding RIFINs, including some from P. falciparum field strains and Plasmodium species infecting gorillas and chimpanzees.

Structural basis of LAIR1 targeting by polymorphic Plasmodium RIFINs.,Xu K, Wang Y, Shen CH, Chen Y, Zhang B, Liu K, Tsybovsky Y, Wang S, Farney SK, Gorman J, Stephens T, Verardi R, Yang Y, Zhou T, Chuang GY, Lanzavecchia A, Piccoli L, Kwong PD Nat Commun. 2021 Jul 9;12(1):4226. doi: 10.1038/s41467-021-24291-6. PMID:34244481^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Xu K, Wang Y, Shen CH, Chen Y, Zhang B, Liu K, Tsybovsky Y, Wang S, Farney SK, Gorman J, Stephens T, Verardi R, Yang Y, Zhou T, Chuang GY, Lanzavecchia A, Piccoli L, Kwong PD. Structural basis of LAIR1 targeting by polymorphic Plasmodium RIFINs. Nat Commun. 2021 Jul 9;12(1):4226. PMID:34244481 doi:10.1038/s41467-021-24291-6

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OCA

[1] Xu K, Wang Y, Shen CH, Chen Y, Zhang B, Liu K, Tsybovsky Y, Wang S, Farney SK, Gorman J, Stephens T, Verardi R, Yang Y, Zhou T, Chuang GY, Lanzavecchia A, Piccoli L, Kwong PD. Structural basis of LAIR1 targeting by polymorphic Plasmodium RIFINs. Nat Commun. 2021 Jul 9;12(1):4226. PMID:34244481 doi:10.1038/s41467-021-24291-6

[1]