8G1C
Crystal structure of polyreactive 3B03 human Fab
Summary for 8G1C
| Entry DOI | 10.2210/pdb8g1c/pdb |
| Descriptor | Heavy chain of monoreactive 3B03 human Fab fragment, Light chain of monoreactive 3B03 human Fab fragment (3 entities in total) |
| Functional Keywords | immunoglobulin g, anti-influenza, monoreactive, immune system |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 93013.48 |
| Authors | Borowska, M.T.,Adams, E.J. (deposition date: 2023-02-01, release date: 2023-10-18, Last modification date: 2024-10-23) |
| Primary citation | Borowska, M.T.,Boughter, C.T.,Bunker, J.J.,Guthmiller, J.J.,Wilson, P.C.,Roux, B.,Bendelac, A.,Adams, E.J. Biochemical and biophysical characterization of natural polyreactivity in antibodies. Cell Rep, 42:113190-113190, 2023 Cited by PubMed Abstract: To become specialized binders, antibodies undergo a process called affinity maturation to maximize their binding affinity. Despite this process, some antibodies retain low-affinity binding to diverse epitopes in a phenomenon called polyreactivity. Here we seek to understand the molecular basis of this polyreactivity in antibodies. Our results highlight that polyreactive antigen-binding fragments (Fabs) bind their targets with low affinities, comparable to T cell receptor recognition of autologous classical major histocompatibility complex. Extensive mutagenic studies find no singular amino acid residue or biochemical property responsible for polyreactive interaction, suggesting that polyreactive antibodies use multiple strategies for engagement. Finally, our crystal structures and all-atom molecular dynamics simulations of polyreactive Fabs show increased rigidity compared to their monoreactive relatives, forming a neutral and accessible platform for diverse antigens to bind. Together, these data support a cooperative strategy of rigid neutrality in establishing the polyreactive status of an antibody molecule. PubMed: 37804505DOI: 10.1016/j.celrep.2023.113190 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.63 Å) |
Structure validation
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