Efalizumab binding to the LFA-1 αL I domain blocks ICAM-1 binding via steric hindrance
العنوان: | Efalizumab binding to the LFA-1 αL I domain blocks ICAM-1 binding via steric hindrance |
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المؤلفون: | Sheng Hou, Jianping Ding, Baozhen Peng, Yajun Guo, Hao Wang, Daipong Zhang, Meilan Zhang, Sheng Li |
بيانات النشر: | National Academy of Sciences, 2009. |
سنة النشر: | 2009 |
مصطلحات موضوعية: | Efalizumab, Intercellular Adhesion Molecule-1, chemical and pharmacologic phenomena, Plasma protein binding, CD11a, Biology, Antibodies, Monoclonal, Humanized, Epitope, Autoimmune Diseases, Epitopes, medicine, Humans, Lymphocyte function-associated antigen 1, Binding site, Multidisciplinary, Binding Sites, Antibodies, Monoclonal, Biological Sciences, Ligand (biochemistry), Molecular biology, Lymphocyte Function-Associated Antigen-1, Cell biology, Cell Migration Inhibition, medicine.drug, Protein Binding |
الوصف: | Lymphocyte function-associated antigen 1 (LFA-1) plays important roles in immune cell adhesion, trafficking, and activation and is a therapeutic target for the treatment of multiple autoimmune diseases. Efalizumab is one of the most efficacious antibody drugs for treating psoriasis, a very common skin disease, through inhibition of the binding of LFA-1 to the ligand intercellular adhesion molecule 1 (ICAM-1). We report here the crystal structures of the Efalizumab Fab alone and in complex with the LFA-1 αLI domain, which reveal the molecular mechanism of inhibition of LFA-1 by Efalizumab. The Fab binds with an epitope on the inserted (I) domain that is distinct from the ligand-binding site. Efalizumab binding blocks the binding of LFA-1 to ICAM-1 via steric hindrance between its light chain and ICAM-1 domain 2 and thus inhibits the activities of LFA-1. These results have important implications for the development of improved antibodies and new therapeutic strategies for the treatment of autoimmune diseases. |
اللغة: | English |
الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d7bb5d93aa7095c0b4773e3daebdfac8Test https://europepmc.org/articles/PMC2657446Test/ |
حقوق: | OPEN |
رقم الانضمام: | edsair.doi.dedup.....d7bb5d93aa7095c0b4773e3daebdfac8 |
قاعدة البيانات: | OpenAIRE |
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