1jps: Difference between revisions
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'''Crystal structure of tissue factor in complex with humanized Fab D3h44''' | '''Crystal structure of tissue factor in complex with humanized Fab D3h44''' | ||
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[[Category: Muller, Y A.]] | [[Category: Muller, Y A.]] | ||
[[Category: Presta, L.]] | [[Category: Presta, L.]] | ||
[[Category: | [[Category: Antigen-antibody recognition]] | ||
[[Category: | [[Category: Blood coagulation]] | ||
[[Category: | [[Category: Crystal structure]] | ||
[[Category: | [[Category: Humanized antibody]] | ||
[[Category: | [[Category: Interface water molecule]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 21:34:18 2008'' | |||
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Revision as of 21:34, 2 May 2008
Crystal structure of tissue factor in complex with humanized Fab D3h44
OverviewOverview
The outstanding importance of the antigen-antibody recognition process for the survival and defence strategy of higher organisms is in sharp contrast to the limited high resolution structural data available on antibody-antigen pairs with antigenic proteins. The limitation is the most severe for structural data not restricted to the antigen-antibody complex but extending to the uncomplexed antigen and antibody. We report the crystal structure of the complex between tissue factor (TF) and the humanized Fab fragment D3h44 at a resolution of 1.85 A together with the structure of uncomplexed D3h44 at the same resolution. In conjunction with the previously reported 1.7 A crystal structure of uncomplexed TF, a unique opportunity is generated to explore details of the recognition process. The TF.D3h44 interface is characterised by a high number of polar interactions, including as may as 46 solvent molecules. Conformational changes upon complex formation are very small and almost exclusively limited to the reorientation of side-chains. The binding epitope is in complete agreement with earlier mutagenesis experiments. A revaluation of two other antibody-antigen pairs reported at similar resolutions, shows that all these complexes are very similar with respect to the solvation of the interface, the number of solvent positions conserved in the uncomplexed and complexed proteins and the number of water molecules expelled from the surface and replaced by hydrophilic atoms from the binding partner upon complex formation. A strategy is proposed on how to exploit this high resolution structural data to guide the affinity maturation of humanised antibodies.
About this StructureAbout this Structure
1JPS is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
The 1.85 A resolution crystal structures of tissue factor in complex with humanized Fab D3h44 and of free humanized Fab D3h44: revisiting the solvation of antigen combining sites., Faelber K, Kirchhofer D, Presta L, Kelley RF, Muller YA, J Mol Biol. 2001 Oct 12;313(1):83-97. PMID:11601848 Page seeded by OCA on Fri May 2 21:34:18 2008