3D5R

Crystal Structure of Efb-C (N138A) / C3d Complex

Summary for 3D5R

• Entry DOI: 10.2210/pdb3d5r/pdb
• Related: 2GOM 2GOX 2NOJ 3D5S
• Descriptor: Complement C3, Fibrinogen-binding protein (3 entities in total)
• Functional Keywords: protein-protein complex, cell adhesion-toxin complex, site-directed mutation, age-related macular degeneration, cleavage on pair of basic residues, complement alternate pathway, complement pathway, disease mutation, glycoprotein, immune response, inflammatory response, innate immunity, phosphoprotein, polymorphism, secreted, thioester bond, cell adhesion/toxin
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted: P01024 A6QG59
• Total number of polymer chains: 4
• Total formula weight: 81387.51

Authors

Geisbrecht, B.V. (deposition date: 2008-05-16, release date: 2008-09-09, Last modification date: 2024-10-16)

Primary citation

Haspel, N.,Ricklin, D.,Geisbrecht, B.V.,Kavraki, L.E.,Lambris, J.D.
Electrostatic contributions drive the interaction between Staphylococcus aureus protein Efb-C and its complement target C3d.
Protein Sci., 17:1894-1906, 2008

PubMed Abstract: The C3-inhibitory domain of Staphylococcus aureus extracellular fibrinogen-binding protein (Efb-C) defines a novel three-helix bundle motif that regulates complement activation. Previous crystallographic studies of Efb-C bound to its cognate subdomain of human C3 (C3d) identified Arg-131 and Asn-138 of Efb-C as key residues for its activity. In order to characterize more completely the physical and chemical driving forces behind this important interaction, we employed in this study a combination of structural, biophysical, and computational methods to analyze the interaction of C3d with Efb-C and the single-point mutants R131A and N138A. Our results show that while these mutations do not drastically affect the structure of the Efb-C/C3d recognition complex, they have significant adverse effects on both the thermodynamic and kinetic profiles of the resulting complexes. We also characterized other key interactions along the Efb-C/C3d binding interface and found an intricate network of salt bridges and hydrogen bonds that anchor Efb-C to C3d, resulting in its potent complement inhibitory properties.

PubMed: 18687868
DOI: 10.1110/ps.036624.108

Experimental method

X-RAY DIFFRACTION (2.1 Å)