+Open data
-Basic information
Entry | Database: SASBDB / ID: SASDA38 |
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Sample | transglutaminase-2 (TGA2)
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Biological species | Homo sapiens (human) |
Citation | Journal: J Biol Chem / Year: 2015 Title: Structural Basis for Antigen Recognition by Transglutaminase 2-specific Autoantibodies in Celiac Disease. Authors: Xi Chen / Kathrin Hnida / Melissa Ann Graewert / Jan Terje Andersen / Rasmus Iversen / Anne Tuukkanen / Dmitri Svergun / Ludvig M Sollid / Abstract: Antibodies to the autoantigen transglutaminase 2 (TG2) are a hallmark of celiac disease. We have studied the interaction between TG2 and an anti-TG2 antibody (679-14-E06) derived from a single gut ...Antibodies to the autoantigen transglutaminase 2 (TG2) are a hallmark of celiac disease. We have studied the interaction between TG2 and an anti-TG2 antibody (679-14-E06) derived from a single gut IgA plasma cell of a celiac disease patient. The antibody recognizes one of four identified epitopes targeted by antibodies of plasma cells of the disease lesion. The binding interface was identified by small angle x-ray scattering, ab initio and rigid body modeling using the known crystal structure of TG2 and the crystal structure of the antibody Fab fragment, which was solved at 2.4 Å resolution. The result was confirmed by testing binding of the antibody to TG2 mutants by ELISA and surface plasmon resonance. TG2 residues Arg-116 and His-134 were identified to be critical for binding of 679-14-E06 as well as other epitope 1 antibodies. In contrast, antibodies directed toward the two other main epitopes (epitopes 2 and 3) were not affected by these mutations. Molecular dynamics simulations suggest interactions of 679-14-E06 with the N-terminal domain of TG2 via the CDR2 and CDR3 loops of the heavy chain and the CDR2 loop of the light chain. In addition there were contacts of the framework 3 region of the heavy chain with the catalytic domain of TG2. The results provide an explanation for the biased usage of certain heavy and light chain gene segments by epitope 1-specific antibodies in celiac disease. |
Contact author |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Models
Model #310 | Type: atomic / Software: CRYSOL / Radius of dummy atoms: 1.90 A / Chi-square value: 1.507984 Search similar-shape structures of this assembly by Omokage search (details) |
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-Sample
Sample | Name: transglutaminase-2 (TGA2) / Specimen concentration: 5.5 mg/ml |
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Buffer | Name: 20 mM Tris 150mM NaCl 1mM EDTA / Concentration: 20.00 mM / pH: 7.2 / Composition: 150mM NaCl, 1mM EDTA |
Entity #176 | Name: TGA / Type: protein / Description: transglutaminase 2 / Formula weight: 79.491 / Num. of mol.: 1 / Source: Homo sapiens Sequence: MGSSHHHHHH SSGLVPRGSH maeelvlerc dleletngrd hhtadlcrek lvvrrgqpfw ltlhfegrny easvdsltfs vvtgpapsqe agtkarfplr daveegdwta tvvdqqdctl slqlttpana piglyrlsle astgyqgssf vlghfillfn awcpadavyl ...Sequence: MGSSHHHHHH SSGLVPRGSH maeelvlerc dleletngrd hhtadlcrek lvvrrgqpfw ltlhfegrny easvdsltfs vvtgpapsqe agtkarfplr daveegdwta tvvdqqdctl slqlttpana piglyrlsle astgyqgssf vlghfillfn awcpadavyl dseeerqeyv ltqqgfiyqg sakfiknipw nfgqfedgil diclilldvn pkflknagrd csrrsspvyv grvvsgmvnc nddqgvllgr wdnnygdgvs pmswigsvdi lrrwknhgcq rvkygqcwvf aavactvlrc lgiptrvvtn ynsahdqnsn llieyfrnef geiqgdksem iwnfhcwves wmtrpdlqpg yegwqaldpt pqeksegtyc cgpvpvraik egdlstkyda pfvfaevnad vvdwiqqddg svhksinrsl ivglkistks vgrderedit htykypegss eereaftran hlnklaekee tgmamrirvg qsmnmgsdfd vfahitnnta eeyvcrlllc artvsyngil gpecgtkyll nlnlepfsek svplcilyek yrdcltesnl ikvrallvep vinsyllaer dlylenpeik irilgepkqk rklvaevslq nplpvalegc tftvegaglt eeqktveipd pveageevkv rmdllplhmg lhklvvnfes dklkavkgfr nviigpa |
-Experimental information
Beam | Instrument name: PETRA III P12 / City: Hamburg / 国: Germany / Type of source: X-ray synchrotron / Wavelength: 0.12 Å / Dist. spec. to detc.: 3.1 mm | |||||||||||||||||||||||||||||||||||||||
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Detector | Name: Pilatus 2M | |||||||||||||||||||||||||||||||||||||||
Scan | Title: transglutaminase 2 (TG2 mixture) / Measurement date: Jan 17, 2015 / Storage temperature: 10 °C / Cell temperature: 10 °C / Exposure time: 0.05 sec. / Number of frames: 20 / Unit: 1/nm /
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Distance distribution function P(R) | Sofotware P(R): GNOM 5.0 / Number of points: 1096 /
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Result | Type of curve: single_conc Comments: Structural basis for antigen recognition by transglutaminase 2-specific autoantibodies in celiac disease --- this is the scattering profile of TG2 by itself that is comprised primarilly of ...Comments: Structural basis for antigen recognition by transglutaminase 2-specific autoantibodies in celiac disease --- this is the scattering profile of TG2 by itself that is comprised primarilly of monomers and higher oligomeric species (monomer 92%; dimer 8% volume fraction.)
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