Loading
PDBj
MenuPDBj@FacebookPDBj@X(formerly Twitter)PDBj@BlueSkyPDBj@YouTubewwPDB FoundationwwPDBDonate
RCSB PDBPDBeBMRBAdv. SearchSearch help

6EHG

complement component C3b in complex with a nanobody

Summary for 6EHG
Entry DOI10.2210/pdb6ehg/pdb
DescriptorComplement 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)
Functional Keywordsprotein complex, inhibitor, complement, complement system, single domain antibody, nanobody, immune system
Biological sourceLama glama (llama)
More
Total number of polymer chains3
Total formula weight190536.01
Authors
Jensen, R.K.,Andersen, K.R.,Gadeberg, T.A.F.,Laursen, N.S.,Andersen, G.R. (deposition date: 2017-09-13, release date: 2018-02-14, Last modification date: 2024-11-13)
Primary citationJensen, 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
Cited by
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
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (2.65 Å)
Structure validation

238582

PDB entries from 2025-07-09

PDB statisticsPDBj update infoContact PDBjnumon