ISDA: 45AS

Deposition Date 2026-08-21

Release Date 2026-10-07

Last Version Date 2026-10-07

Entry Detail

PDB ID:

45AS

Keywords:

IMMUNE SYSTEM

Title:

Crystal structure of C11 nanobody in complex with human MR1-Ac-6-FP

Biological Source:

Source Organism(s):

Homo sapiens (Taxon ID: 9606)

Expression System(s):

Escherichia coli

Method Details:

Experimental Method:

X-RAY DIFFRACTION

Resolution:

3.14 Å

R-Value Free:

0.22

R-Value Work:

0.20

R-Value Observed:

0.20

Space Group:

P 32 1 2

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Macromolecular Entities

Structures with similar UniProt ID

Structural Superimposition Protein Blast

Polymer Type:polypeptide(L)
Molecule:Major histocompatibility comp
Gene (Uniprot):MR1
Chain IDs:A
Chain Length:271
Number of Molecules:1
Biological Source:Homo sapiens

UniProt ID:Q95460 Pfam ID:PF00129, PF07654

Structures with similar UniProt ID

Structural Superimposition Protein Blast

Polymer Type:polypeptide(L)
Molecule:Beta-2-microglobulin
Gene (Uniprot):B2M
Chain IDs:B
Chain Length:100
Number of Molecules:1
Biological Source:Homo sapiens

UniProt ID:P61769 Pfam ID:PF07654

Polymer Type:polypeptide(L)
Molecule:C11 nanoody
Chain IDs:C
Chain Length:128
Number of Molecules:1
Biological Source:Homo sapiens

Ligand Molecules

30W

Primary Citation

Specific targeting of MR1-antigen complexes using nanobodies.

Hussain, H.S, Redmond, S.J, Awad, W, Xu, C, Soliman, C, Wang, H, Zhang, Y, Ciacchi, L, Gonzalez, A.P, Mak, J.Y.W, Fairlie, D.P, McCluskey, J, Corbett, A.J, Uldrich, A.P, Rossjohn, J, Godfrey, D.I, Koay, H.F, Gherardin, N.A.Show

Sci Immunol 11 eaeb8726 eaeb8726 (2026)

PMID: 42789664 DOI: 10.1126/sciimmunol.aeb8726

Abstact

T cell receptor mimic (TCRm) antibodies that bind peptide-human leukocyte antigen complexes have great therapeutic potential. Major histocompatibility complex class I-related protein 1 (MR1) exhibits limited polymorphism and presents conserved metabolites, such as 5-OP-RU, derived from microbial riboflavin biosynthesis. Whether antibodies targeting such MR1-5-OP-RU complexes can be generated remains unclear. Using yeast display technology, nanobodies with high affinity toward the MR1-5-OP-RU complex were generated. These nanobodies can bind both mouse and human MR1-5-OP-RU and inhibit mucosal-associated invariant T (MAIT) cell responses to 5-OP-RU and bacterial challenge, demonstrating in vitro and in vivo bioactivity. We also solved the crystal structures of the lead nanobody in complex with MR1 antigens and demonstrated that the nanobody cobound MR1 and 5-OP-RU, akin to a TCRm antibody. Last, we engineered bispecific antibodies targeting both MR1-5-OP-RU and CD3 that drive broad T cell killing of bacterially infected cells as well as tumor cells treated with 5-OP-RU, providing evidence for immune redirection via MR1-targeting TCRm-based nanobodies.

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Primary Citation of related structures

Abstact

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