7JZ4

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

Summary for 7JZ4

• Entry DOI: 10.2210/pdb7jz4/pdb
• Descriptor: MGD21 heavy chain, MGD21 light chain, PHOSPHATE ION, ... (5 entities in total)
• Functional Keywords: lair1, insertion, antibody, rifin, malaria, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 4
• Total formula weight: 126126.51

Authors

Xu, K.,Kwong, P.D. (deposition date: 2020-09-01, release date: 2021-05-26, Last modification date: 2024-10-09)

Primary citation

Xu, K.,Wang, Y.,Shen, C.H.,Chen, Y.,Zhang, B.,Liu, K.,Tsybovsky, Y.,Wang, S.,Farney, S.K.,Gorman, J.,Stephens, T.,Verardi, R.,Yang, Y.,Zhou, T.,Chuang, G.Y.,Lanzavecchia, A.,Piccoli, L.,Kwong, P.D.
Structural basis of LAIR1 targeting by polymorphic Plasmodium RIFINs.
Nat Commun, 12:4226-4226, 2021

PubMed Abstract: 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.

PubMed: 34244481
DOI: 10.1038/s41467-021-24291-6

Experimental method

X-RAY DIFFRACTION (2.747 Å)