5GKR

Crystal structure of SLE patient-derived anti-DNA antibody in complex with oligonucleotide

Summary for 5GKR

• Entry DOI: 10.2210/pdb5gkr/pdb
• Related: 5GKS
• Descriptor: IgG2, Fab (heavy chain), lambda, Fab (light chain), DNA (5'-D(P*TP*TP*TP*T)-3'), ... (4 entities in total)
• Functional Keywords: antibody, lupus, dna, fab, immune system-dna complex, immune system/dna
• Biological source: Homo sapiens; More
• Total number of polymer chains: 5
• Total formula weight: 93862.87

Authors

Arimori, T.,Sakakibara, S.,Kikutani, H.,Takagi, J. (deposition date: 2016-07-05, release date: 2017-07-05, Last modification date: 2024-10-23)

Primary citation

Sakakibara, S.,Arimori, T.,Yamashita, K.,Jinzai, H.,Motooka, D.,Nakamura, S.,Li, S.,Takeda, K.,Katayama, J.,El Hussien, M.A.,Narazaki, M.,Tanaka, T.,Standley, D.M.,Takagi, J.,Kikutani, H.
Clonal evolution and antigen recognition of anti-nuclear antibodies in acute systemic lupus erythematosus
Sci Rep, 7:16428-16428, 2017

PubMed Abstract: The evolutional process of disease-associated autoantibodies in systemic lupus erythematosus (SLE) remains to be established. Here we show intraclonal diversification and affinity maturation of anti-nuclear antibody (ANA)-producing B cells in SLE. We identified a panel of monoclonal ANAs recognizing nuclear antigens, such as double-stranded DNA (dsDNA) and ribonucleoproteins (RNPs) from acute SLE subjects. These ANAs had relatively few, but nonetheless critical mutations. High-throughput immunoglobulin sequencing of blood lymphocytes disclosed the existence of sizable ANA lineages shearing critical mutations intraclonally. We further focused on anti-DNA antibodies, which are capable to bind to both single-stranded (ss) and dsDNA at high affinity. Crystal structure and biochemical analysis confirmed a direct role of the mutations in the acquisition of DNA reactivity and also revealed that these anti-DNA antibodies recognized an unpaired region within DNA duplex. Our study unveils the unique properties of high-affinity anti-DNA antibodies that are generated through antigen-driven affinity maturation in acute phase of SLE.

PubMed: 29180749
DOI: 10.1038/s41598-017-16681-y

Experimental method

X-RAY DIFFRACTION (2.1 Å)