The 2.3A crystal structure of the antibody Fab HPC-4 in complex with calcium and the epitope peptide.

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dc.contributor.advisorMather, Timothy,en_US
dc.contributor.advisorNollert, Matthias U.,en_US
dc.contributor.authorGarteiser, Philippe.en_US
dc.date.accessioned2013-08-16T12:20:39Z
dc.date.available2013-08-16T12:20:39Z
dc.date.issued2007en_US
dc.description.abstractThe murine monoclonal antibody HPC-4, directed against the activation region of the human anticoagulant zymogen protein C (PC), is one of the few immunoglobulins known to display calcium-dependent antigen binding. Unlike the more common class of antibodies that merely recognize a calcium-bound conformation of their antigen, HPC-4 interacts directly with calcium in the high affinity PC-HPC-4 complex.en_US
dc.description.abstractMetal ions can have considerable affinities for proteins, and give rise to geometric constraints that are often taken advantage of in protein-protein interactions. The coordination shell of metal ions can be filled by atoms provided by two different proteins, resulting in a high affinity protein complex. Surprisingly, this highly efficient binding strategy is rarely observed in immunoglobulins, despite the great number of known antibody structures determined in complex with their protein antigens.en_US
dc.description.abstractThe structure reveals a mode of calcium binding which underlies a novel mechanism of metal aided antigen recognition. The ion is located at the antibodyantigen interface, where it functions both as an electrostatic bridge and as a conformational effector of the antibody. The antigen is further stabilized by an extensive and diverse array of interactions spanning a large surface area of contact. Our results provide a structural explanation for many of the observed characteristics of HPC-4, the first member of a unique class of calcium binding antibodies. As such, it represents a significant contribution to the study of interfacial metals and the structural biology of antibodies.en_US
dc.description.abstractTo provide a structural understanding of HPC-4 function and of the particular antibody class to which it belongs, we have solved the X-ray crystal structure of the HPC-4 Fab fragment in ternary complex with its epitope peptide in the presence of calcium at a resolution of 2.3A. Within the crystal, the antigen-binding region is undistorted by crystalline lattice contacts. All complementarity-determining regions and the peptide antigen have well-defined electron density.en_US
dc.format.extentvi, 137 leaves :en_US
dc.identifier.urihttp://hdl.handle.net/11244/1189
dc.noteAdvisers: Matthias U. Nollert; Timothy Mather.en_US
dc.noteSource: Dissertation Abstracts International, Volume: 68-04, Section: B, page: 2481.en_US
dc.subjectImmunoglobulins.en_US
dc.subjectEngineering, Biomedical.en_US
dc.subjectMetal ions.en_US
dc.subjectAntigen-antibody reactions.en_US
dc.thesis.degreePh.D.en_US
dc.thesis.degreeDisciplineSchool of Chemical, Biological and Materials Engineeringen_US
dc.titleThe 2.3A crystal structure of the antibody Fab HPC-4 in complex with calcium and the epitope peptide.en_US
dc.typeThesisen_US
ou.groupCollege of Engineering::School of Chemical, Biological and Materials Engineering
ou.identifier(UMI)AAI3261112en_US

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