2ok0: Difference between revisions
No edit summary |
No edit summary |
||
| Line 4: | Line 4: | ||
==Overview== | ==Overview== | ||
DNA recognition by antibodies is a key feature of autoimmune diseases, yet | DNA recognition by antibodies is a key feature of autoimmune diseases, yet model systems with structural information are very limited. The monoclonal antibody ED-10 recognizes one of the strands of the DNA duplex used in the immunogenic complex. Modifications of the 5' end decrease the binding affinity and short oligonucleotides retain high binding affinity. We determined crystal structures for the Fab bound to a 6-mer oligonucleotide containing the specific sequence that raised the antibody and compared it with the unliganded Fab. Only the first two bases from the 5' end (dTdC) display electron density and we observe four key hydrogen bonds at the interface. The thymine ring is stacked between TrpH50 and TrpH95, and the cytosine ring is packed against TyrL32. Upon DNA binding, TyrH97 and TrpH95 rearrange to allow subnanomolar binding affinity, five orders of magnitude higher than other reported complexes, possibly because of having gone through affinity maturation. This structure represents the first bona fide antibody DNA immunogen complex described in atomic detail. | ||
==About this Structure== | ==About this Structure== | ||
| Line 13: | Line 13: | ||
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Prat-Gay, G | [[Category: Prat-Gay, G de.]] | ||
[[Category: Sanguineti, S.]] | [[Category: Sanguineti, S.]] | ||
[[Category: Stanfield, R | [[Category: Stanfield, R L.]] | ||
[[Category: Wilson, I | [[Category: Wilson, I A.]] | ||
[[Category: immunoglobulin fold]] | [[Category: immunoglobulin fold]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:19:27 2008'' | ||
Revision as of 19:19, 21 February 2008
|
Fab ED10-DNA complex
OverviewOverview
DNA recognition by antibodies is a key feature of autoimmune diseases, yet model systems with structural information are very limited. The monoclonal antibody ED-10 recognizes one of the strands of the DNA duplex used in the immunogenic complex. Modifications of the 5' end decrease the binding affinity and short oligonucleotides retain high binding affinity. We determined crystal structures for the Fab bound to a 6-mer oligonucleotide containing the specific sequence that raised the antibody and compared it with the unliganded Fab. Only the first two bases from the 5' end (dTdC) display electron density and we observe four key hydrogen bonds at the interface. The thymine ring is stacked between TrpH50 and TrpH95, and the cytosine ring is packed against TyrL32. Upon DNA binding, TyrH97 and TrpH95 rearrange to allow subnanomolar binding affinity, five orders of magnitude higher than other reported complexes, possibly because of having gone through affinity maturation. This structure represents the first bona fide antibody DNA immunogen complex described in atomic detail.
About this StructureAbout this Structure
2OK0 is a Protein complex structure of sequences from Mus musculus. Full crystallographic information is available from OCA.
ReferenceReference
Specific recognition of a DNA immunogen by its elicited antibody., Sanguineti S, Centeno Crowley JM, Lodeiro Merlo MF, Cerutti ML, Wilson IA, Goldbaum FA, Stanfield RL, de Prat-Gay G, J Mol Biol. 2007 Jun 29;370(1):183-95. Epub 2007 Apr 24. PMID:17512945
Page seeded by OCA on Thu Feb 21 18:19:27 2008