9UVI

Crystal structure of beta 2 microglobulin in complex with antibody BBM.1

Summary for 9UVI

• Entry DOI: 10.2210/pdb9uvi/pdb
• Descriptor: BBM.1 light chain, BBM.1 heavy chain, Beta-2-microglobulin, ... (4 entities in total)
• Functional Keywords: immune system
• Biological source: Mus musculus; More
• Total number of polymer chains: 3
• Total formula weight: 36070.32

Authors

Wei, P.C.,Wu, J.J. (deposition date: 2025-05-10, release date: 2025-09-03, Last modification date: 2025-09-17)

Primary citation

Wu, J.,Zeng, F.,Wang, X.,Wei, P.
Crystal structure of the beta 2 -microglobulin-BBM.1 antibody complex reveals the molecular basis of antigen recognition.
Acta Crystallogr D Struct Biol, 81:473-481, 2025

PubMed Abstract: β-Microglobulin (βM) is an essential component of major histocompatibility complex class I (MHC-I) molecules, with a well established canonical role in immune surveillance. Beyond its classical functions, accumulating evidence has highlighted βM as a multifaceted biomarker, with elevated serum levels closely associated with disease burden and prognosis in metabolic disorders, malignancies, autoimmune diseases and central nervous system conditions. In this study, we resolved the crystal structure of human βM in complex with the mouse monoclonal antibody BBM.1 at 2.50 Å resolution using X-ray crystallography. Structural analysis revealed that BBM.1 binds βM through multiple CDRs, recognizing key surface residues including Glu36, Asp38, Lys41, Asn42, Glu44, Arg45, Glu47 and Arg81. The interaction is anchored by a central hydrophobic core formed by Trp32 (light chain), Trp99 (heavy chain) and Ile92 (βM), which is deeply buried in the interface. Surrounding this core is a well organized polar interaction network composed of hydrogen bonds and salt bridges, primarily involving βM residues Lys41, Glu44, Arg45 and Glu47. Notably, the Arg45 residue deeply embeds into the antibody-binding pocket, forming several crucial interactions. These findings not only validate previous biochemical and mutational data but also identify new epitope residues, providing a structural foundation for the development and optimization of precision therapeutic strategies targeting βM.

PubMed: 40748259
DOI: 10.1107/S2059798325006370

Experimental method

X-RAY DIFFRACTION (2.5 Å)