2A73

Human Complement Component C3

Summary for 2A73

• Entry DOI: 10.2210/pdb2a73/pdb
• Descriptor: Complement C3, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-3)-[beta-D-mannopyranose-(1-6)]alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: intact thioester, immune system
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted: P01024 P01024
• Total number of polymer chains: 2
• Total formula weight: 185685.22

Authors

Janssen, B.J.C.,Huizinga, E.G.,Raaijmakers, H.C.A.,Roos, A.,Daha, M.R.,Nilsson-Ekdahl, K.,Nilsson, B.,Gros, P. (deposition date: 2005-07-04, release date: 2005-09-27, Last modification date: 2024-10-30)

Primary citation

Janssen, B.J.,Huizinga, E.G.,Raaijmakers, H.C.,Roos, A.,Daha, M.R.,Nilsson-Ekdahl, K.,Nilsson, B.,Gros, P.
Structures of complement component C3 provide insights into the function and evolution of immunity.
Nature, 437:505-511, 2005

PubMed Abstract: The mammalian complement system is a phylogenetically ancient cascade system that has a major role in innate and adaptive immunity. Activation of component C3 (1,641 residues) is central to the three complement pathways and results in inflammation and elimination of self and non-self targets. Here we present crystal structures of native C3 and its final major proteolytic fragment C3c. The structures reveal thirteen domains, nine of which were unpredicted, and suggest that the proteins of the alpha2-macroglobulin family evolved from a core of eight homologous domains. A double mechanism prevents hydrolysis of the thioester group, essential for covalent attachment of activated C3 to target surfaces. Marked conformational changes in the alpha-chain, including movement of a critical interaction site through a ring formed by the domains of the beta-chain, indicate an unprecedented, conformation-dependent mechanism of activation, regulation and biological function of C3.

PubMed: 16177781
DOI: 10.1038/nature04005

Experimental method

X-RAY DIFFRACTION (3.3 Å)