دورية أكاديمية
أعرض في EDS

Structures of a pan-specific antagonist antibody complexed to different isoforms of TGFβ reveal structural plasticity of antibody-antigen interactions.

التفاصيل البيبلوغرافية
العنوان: Structures of a pan-specific antagonist antibody complexed to different isoforms of TGFβ reveal structural plasticity of antibody-antigen interactions.
المؤلفون: Moulin A; Sanofi Biotherapeutics, Framingham, Massachusetts, USA., Mathieu M, Lawrence C, Bigelow R, Levine M, Hamel C, Marquette JP, Le Parc J, Loux C, Ferrari P, Capdevila C, Dumas J, Dumas B, Rak A, Bird J, Qiu H, Pan CQ, Edmunds T, Wei RR
المصدر: Protein science : a publication of the Protein Society [Protein Sci] 2014 Dec; Vol. 23 (12), pp. 1698-707. Date of Electronic Publication: 2014 Sep 26.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Cold Spring Harbor Laboratory Press Country of Publication: United States NLM ID: 9211750 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1469-896X (Electronic) Linking ISSN: 09618368 NLM ISO Abbreviation: Protein Sci Subsets: MEDLINE
أسماء مطبوعة: Publication: 2001- : Woodbury, NY : Cold Spring Harbor Laboratory Press
Original Publication: New York, N.Y. : Cambridge University Press, c1992-
مواضيع طبية MeSH: Antibodies, Monoclonal/*chemistry , Antibodies, Monoclonal/*immunology , Antibody Specificity/*immunology , Antigen-Antibody Reactions/*immunology , Transforming Growth Factor beta/*chemistry , Transforming Growth Factor beta/*immunology, Antibodies, Monoclonal, Humanized ; Antibodies, Neutralizing/chemistry ; Antibodies, Neutralizing/immunology ; Crystallography, X-Ray ; Humans ; Immunoglobulin Fab Fragments/chemistry ; Immunoglobulin Fab Fragments/immunology ; Models, Molecular ; Protein Conformation ; Protein Isoforms/chemistry ; Protein Isoforms/immunology ; Single-Chain Antibodies/chemistry ; Single-Chain Antibodies/immunology
مستخلص: Various important biological pathways are modulated by TGFβ isoforms; as such they are potential targets for therapeutic intervention. Fresolimumab, also known as GC1008, is a pan-TGFβ neutralizing antibody that has been tested clinically for several indications including an ongoing trial for focal segmental glomerulosclerosis. The structure of the antigen-binding fragment of fresolimumab (GC1008 Fab) in complex with TGFβ3 has been reported previously, but the structural capacity of fresolimumab to accommodate tight interactions with TGFβ1 and TGFβ2 was insufficiently understood. We report the crystal structure of the single-chain variable fragment of fresolimumab (GC1008 scFv) in complex with target TGFβ1 to a resolution of 3.00 Å and the crystal structure of GC1008 Fab in complex with TGFβ2 to 2.83 Å. The structures provide further insight into the details of TGFβ recognition by fresolimumab, give a clear indication of the determinants of fresolimumab pan-specificity and provide potential starting points for the development of isoform-specific antibodies using a fresolimumab scaffold.
(© 2014 The Protein Society.)
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فهرسة مساهمة: Keywords: X-ray crystallography; antibody; fibrosis; ligand; pan-specific inhibitor; protein complex; receptor; transforming growth factor beta
سلسلة جزيئية: PDB 4KV5; 4KXZ
المشرفين على المادة: 0 (Antibodies, Monoclonal)
0 (Antibodies, Monoclonal, Humanized)
0 (Antibodies, Neutralizing)
0 (Immunoglobulin Fab Fragments)
0 (Protein Isoforms)
0 (Single-Chain Antibodies)
0 (Transforming Growth Factor beta)
375142VBIA (fresolimumab)
تواريخ الأحداث: Date Created: 20140912 Date Completed: 20151001 Latest Revision: 20211021
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC4253810
DOI: 10.1002/pro.2548
PMID: 25209176
قاعدة البيانات: MEDLINE
الوصف
تدمد:1469-896X
DOI:10.1002/pro.2548