6BXA

Crystal structure of N-terminal fragment of Zebrafish Toll-Like Receptor 5 (TLR5) with Lamprey Variable Lymphocyte Receptor 2 (VLR2) bound

Summary for 6BXA

• Entry DOI: 10.2210/pdb6bxa/pdb
• Descriptor: Toll-like receptor 5b, Variable lymphocyte receptor B chimera, Variable Lymphocyte Receptor 2, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: vlr, leucine-rich repeat, antibody, immune system
• Biological source: Danio rerio (Zebrafish); More
• Total number of polymer chains: 4
• Total formula weight: 150280.95

Authors

Gunn, R.J.,Wilson, I.A.,Cooper, M.D.,Herrin, B.R. (deposition date: 2017-12-18, release date: 2018-05-09, Last modification date: 2024-10-16)

Primary citation

Gunn, R.J.,Herrin, B.R.,Acharya, S.,Cooper, M.D.,Wilson, I.A.
VLR Recognition of TLR5 Expands the Molecular Characterization of Protein Antigen Binding by Non-Ig-based Antibodies.
J. Mol. Biol., 430:1350-1367, 2018

PubMed Abstract: Variable lymphocyte receptors (VLRs) are unconventional adaptive immune receptors relatively recently discovered in the phylogenetically ancient jawless vertebrates, lamprey and hagfish. VLRs bind antigens using a leucine-rich repeat fold and are the only known adaptive immune receptors that do not utilize an immunoglobulin fold for antigen recognition. While immunoglobulin antibodies have been studied extensively, there are comparatively few studies on antigen recognition by VLRs, particularly for protein antigens. Here we report isolation, functional and structural characterization of three VLRs that bind the protein toll-like receptor 5 (TLR5) from zebrafish. Two of the VLRs block binding of TLR5 to its cognate ligand flagellin in functional assays using reporter cells. Co-crystal structures revealed that these VLRs bind to two different epitopes on TLR5, both of which include regions involved in flagellin binding. Our work here demonstrates that the lamprey adaptive immune system can be used to generate high-affinity VLR clones that recognize different epitopes and differentially impact natural ligand binding to a protein antigen.

PubMed: 29596914
DOI: 10.1016/j.jmb.2018.03.016

Experimental method

X-RAY DIFFRACTION (2.298 Å)