2JG9

Crystallographic structure of human C1q globular heads (P1)

Summary for 2JG9

• Entry DOI: 10.2210/pdb2jg9/pdb
• Related: 1PK6 2JG8
• Descriptor: Complement C1q subcomponent subunit A, Complement C1q subcomponent subunit B, Complement C1q subcomponent subunit C, ... (5 entities in total)
• Functional Keywords: polymorphism, glycoprotein, phagocytosis, disease mutation, complement pathway, immune system, cell surface molecule, pyrrolidone carboxylic acid, hydroxylation, innate immunity, immune response, collagen, tolerance, apopotosis, complement
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 6
• Total formula weight: 89967.87

Authors

Paidassi, H.,Tacnet-Delorme, P.,Garlatti, V.,Darnault, C.,Ghebrehiwet, B.,Gaboriaud, C.,Arlaud, G.J.,Frachet, P. (deposition date: 2007-02-09, release date: 2008-02-19, Last modification date: 2024-10-23)

Primary citation

Paidassi, H.,Tacnet-Delorme, P.,Garlatti, V.,Darnault, C.,Ghebrehiwet, B.,Gaboriaud, C.,Arlaud, G.J.,Frachet, P.
C1Q Binds Phosphatidylserine and Likely Acts as a Multiligand-Bridging Molecule in Apoptotic Cell Recognition.
J.Immunol., 180:2329-2338, 2008

PubMed Abstract: Efficient apoptotic cell clearance is critical for maintenance of tissue homeostasis, and to control the immune responses mediated by phagocytes. Little is known about the molecules that contribute "eat me" signals on the apoptotic cell surface. C1q, the recognition unit of the C1 complex of complement, also senses altered structures from self and is a major actor of immune tolerance. HeLa cells were rendered apoptotic by UV-B treatment and a variety of cellular and molecular approaches were used to investigate the nature of the target(s) recognized by C1q. Using surface plasmon resonance, C1q binding was shown to occur at early stages of apoptosis and to involve recognition of a cell membrane component. C1q binding and phosphatidylserine (PS) exposure, as measured by annexin V labeling, proceeded concomitantly, and annexin V inhibited C1q binding in a dose-dependent manner. As shown by cosedimentation, surface plasmon resonance, and x-ray crystallographic analyses, C1q recognized PS specifically and avidly (K(D) = 3.7-7 x 10(-8) M), through multiple interactions between its globular domain and the phosphoserine group of PS. Confocal microscopy revealed that the majority of the C1q molecules were distributed in membrane patches where they colocalized with PS. In summary, PS is one of the C1q ligands on apoptotic cells, and C1q-PS interaction takes place at early stages of apoptosis, in newly organized membrane patches. Given its versatile recognition properties, these data suggest that C1q has the unique ability to sense different markers which collectively would provide strong eat me signals, thereby allowing efficient apoptotic cell removal.

PubMed: 18250442
DOI: 10.4049/jimmunol.180.4.2329

Experimental method

X-RAY DIFFRACTION (1.9 Å)