6EHG

complement component C3b in complex with a nanobody

6EHG の概要

• エントリーDOI: 10.2210/pdb6ehg/pdb
• 分子名称: Complement C3, hC3Nb1, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• 機能のキーワード: protein complex, inhibitor, complement, complement system, single domain antibody, nanobody, immune system
• 由来する生物種: Lama glama (llama); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 190536.01

構造登録者

Jensen, R.K.,Andersen, K.R.,Gadeberg, T.A.F.,Laursen, N.S.,Andersen, G.R. (登録日: 2017-09-13, 公開日: 2018-02-14, 最終更新日: 2024-11-13)

主引用文献

Jensen, R.K.,Pihl, R.,Gadeberg, T.A.F.,Jensen, J.K.,Andersen, K.R.,Thiel, S.,Laursen, N.S.,Andersen, G.R.
A potent complement factor C3-specific nanobody inhibiting multiple functions in the alternative pathway of human and murine complement.
J. Biol. Chem., 293:6269-6281, 2018

PubMed Abstract: The complement system is a complex, carefully regulated proteolytic cascade for which suppression of aberrant activation is of increasing clinical relevance, and inhibition of the complement alternative pathway is a subject of intense research. Here, we describe the nanobody hC3Nb1 that binds to multiple functional states of C3 with subnanomolar affinity. The nanobody causes a complete shutdown of alternative pathway activity in human and murine serum when present in concentrations comparable with that of C3, and hC3Nb1 is shown to prevent proconvertase assembly, as well as binding of the C3 substrate to C3 convertases. Our crystal structure of the C3b-hC3Nb1 complex and functional experiments demonstrate that proconvertase formation is blocked by steric hindrance between the nanobody and an Asn-linked glycan on complement factor B. In addition, hC3Nb1 is shown to prevent factor H binding to C3b, rationalizing its inhibition of factor I activity. Our results identify hC3Nb1 as a versatile, inexpensive, and powerful inhibitor of the alternative pathway in both human and murine model systems of complement activation.

PubMed: 29497000
DOI: 10.1074/jbc.RA117.001179

実験手法

X-RAY DIFFRACTION (2.65 Å)