9DMX

Crystal structure of shark UrIg2 V-C1-C2-C3 domains

Summary for 9DMX

• Entry DOI: 10.2210/pdb9dmx/pdb
• Descriptor: UrIg2 V-C1-C2-C3, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: shark, immune receptor, immune system
• Biological source: Ginglymostoma cirratum
• Total number of polymer chains: 2
• Total formula weight: 104209.42

Authors

Stanfield, R.L.,Wilson, I.A. (deposition date: 2024-09-16, release date: 2025-07-23)

Primary citation

Flajnik, M.F.,Stanfield, R.L.,Verissimo, A.,Neely, H.R.,Munoz-Merida, A.,Criscitiello, M.F.,Wilson, I.A.,Ohta, Y.
Origin of immunoglobulins and T cell receptors: A candidate gene for invasion by the RAG transposon.
Sci Adv, 11:eadw1273-eadw1273, 2025

PubMed Abstract: Rearranging antigen receptors (AgRs) arose when a variable (V) domain exon was invaded by the recombination-activating gene (RAG) transposon ~500 million years ago. We show here that the elasmobranch immunoglobulin heavy (IgH) isotypes-IgM, IgW, and IgNAR-are linked near the αδ T cell receptor (TCRαδ) locus. This linkage presages the emergence of the osteichthyan IgH translocon arrangement and clarifies the relationship between IgH and TCRδs. Recently, we reported , a nonrearranging, elasmobranch major histocompatibility complex (MHC)-linked AgR gene. Here, we describe a nonrearranging paralogue, , linked to this IgM/IgNAR/IgW/TCRαδ gene cluster in an AgR complex (AgRC). UrIg2 amino-terminal domains make homodimers where the C2-C3 structure resembles IgGFc. A relative of the UrIg2 V domain exon was invaded by the RAG transposon, revealing the genesis of the adaptive immune system. Our data indicate that an ancestral chromosome encoded an AgR precursor, undergoing RAG-mediated rearrangement after genome-wide duplication on one chromosome and retaining nonrearranging relics in the MHC and AgRC.

PubMed: 40614193
DOI: 10.1126/sciadv.adw1273

Experimental method

X-RAY DIFFRACTION (2.81 Å)