小柯机器人

英国牛津大学Matthew K. Higgins研究组解析出RIFIN介导LILRB1激活的结构基础。相关论文于2020年7月10日在线发表在《自然》杂志上。

Title: Structural basis for RIFIN-mediated activation of LILRB1 in malaria

Author: Thomas E. Harrison, Alexander M. Mrch, James H. Felce, Akihito Sakoguchi, Adam J. Reid, Hisashi Arase, Michael L. Dustin, Matthew K. Higgins

Issue&Volume: 2020-07-10

Abstract: The Plasmodium species that cause malaria are obligate intracellular parasites, and disease symptoms occur as they replicate within human blood. Despite risking immune detection, the parasite delivers proteins that bind host receptors to infected erythrocyte surfaces. In the causative agent of the most deadly human malaria, Plasmodium falciparum, RIFINs form the largest erythrocyte surface protein family1. Some RIFINs can bind inhibitory immune receptors, acting as targets for unusual antibodies containing a LAIR1 ectodomain2–4, or as ligands for LILRB15. RIFINs stimulate LILRB1 activation and signalling5, thereby potentially dampening human immune responses. To understand this process, we determined a structure of a RIFIN bound to LILRB1. We show that the RIFIN mimics the natural activating ligand of LILRB1, MHC class I, in its LILRB1-binding mode. A single RIFIN mutation disrupts the complex, blocks LILRB1 binding by all tested RIFINs and abolishes signalling in a reporter assay. In a supported lipid bilayer system, which mimics NK cell activation by antibody-dependent cell-mediated cytotoxicity, both RIFIN and MHC are recruited to the NK cell immunological synapse and reduce cell activation, as measured by perforin mobilisation. Therefore, LILRB1-binding RIFINs mimic the binding mode of the natural ligand of LILRB1 and suppress NK cell function.

DOI: 10.1038/s41586-020-2530-3

Source: https://www.nature.com/articles/s41586-020-2530-3

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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