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000842941 1001_ $$0P:(DE-Juel1)174077$$aYerabham, Antony Sravan Kumar$$b0$$ufzj
000842941 245__ $$aBiophysical insights from a single chain camelid antibody directed against the disrupted in schizophrenia 1 protein
000842941 260__ $$aLawrence, Kan.$$bPLoS$$c2018
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000842941 520__ $$aAccumulating evidence suggests an important role for the Disrupted-in-Schizophrenia 1 (DISC1) protein in neurodevelopment and chronic mental illness. In particular, the C-terminal 300 amino acids of DISC1 have been found to mediate important protein-protein interactions and to harbor functionally important phosphorylation sites and disease-associated polymorphisms. However, long disordered regions and oligomer-forming subdomains have so far impeded structural analysis. VHH domains derived from camelid heavy chain only antibodies are minimal antigen binding modules with appreciable solubility and stability, which makes them well suited for the stabilizing proteins prior to structural investigation. Here, we report on the generation of a VHH domain derived from an immunized Lama glama, displaying high affinity for the human DISC1 C region (aa 691–836), and its characterization by surface plasmon resonance, size exclusion chromatography and immunological techniques. The VHH-DISC1 (C region) complex was also used for structural investigation by small angle X-ray scattering analysis. In combination with molecular modeling, these data support predictions regarding the three-dimensional fold of this DISC1 segment as well as its steric arrangement in complex with our VHH antibody.
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000842941 7001_ $$0P:(DE-HGF)0$$aMüller-Schiffmann, Andreas$$b1
000842941 7001_ $$0P:(DE-Juel1)162487$$aZiehm, Tamar$$b2$$ufzj
000842941 7001_ $$0P:(DE-Juel1)140278$$aStadler, Andreas$$b3$$ufzj
000842941 7001_ $$0P:(DE-HGF)0$$aKöber, Sabrina$$b4
000842941 7001_ $$0P:(DE-HGF)0$$aIndurkhya, Xela$$b5
000842941 7001_ $$0P:(DE-HGF)0$$aMarreiros, Rita$$b6
000842941 7001_ $$0P:(DE-HGF)0$$aTrossbach, Svenja$$b7
000842941 7001_ $$0P:(DE-HGF)0$$aBradshaw, Nicholas$$b8
000842941 7001_ $$0P:(DE-HGF)0$$aPrikulis, Ingrid$$b9
000842941 7001_ $$0P:(DE-Juel1)132029$$aWillbold, Dieter$$b10$$ufzj
000842941 7001_ $$0P:(DE-Juel1)131988$$aWeiergräber, Oliver H.$$b11$$ufzj
000842941 7001_ $$0P:(DE-HGF)0$$aKorth, Carsten$$b12$$eCorresponding author
000842941 773__ $$0PERI:(DE-600)2267670-3$$a10.1371/journal.pone.0191162$$gVol. 13, no. 1, p. e0191162 -$$n1$$pe0191162 -$$tPLoS one$$v13$$x1932-6203$$y2018
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