1xf2: Difference between revisions

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[[Image:1xf2.gif|left|200px]]<br />

[[Image:1xf2.gif|left|200px]]<br /><applet load="1xf2" size="350" color="white" frame="true" align="right" spinBox="true"

<applet load="1xf2" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

caption="1xf2, resolution 2.30Å" />

'''Structure of Fab DNA-1 complexed with dT3'''<br />

==Overview==

Anti-DNA antibodies play important roles in the pathogenesis of autoimmune, diseases. They also represent a unique and relatively unexplored class of, DNA-binding protein. Here, we present a study of conformational changes, induced by DNA binding to an anti-ssDNA Fab known as DNA-1. Three crystal, structures are reported: a complex of DNA-1 bound to dT3, and two, structures of the ligand-free Fab. One of the ligand-free structures was, determined from crystals exhibiting perfect hemihedral twinning, and the, details of structure determination are provided. Unexpectedly, five, residues (H97-H100A) in the apex of heavy chain, complementarity-determining region 3 (HCDR3) are disordered in both, ligand-free structures. Ligand binding also caused a 2-4A shift of the, backbone of Tyr L92 and ordering of the L92 side-chain. In contrast, these, residues are highly ordered in the Fab/dT3 complex, where Tyr H100 and Tyr, H100A form intimate stacking interactions with DNA bases, and L92 forms, the 5' end of the binding site. The structures suggest that HCDR3 is very, flexible and adopts multiple conformations in the ligand-free state. These, results are discussed in terms of induced fit and pre-existing equilibrium, theories of ligand binding. Our results allow new interpretations of, existing thermodynamic and mutagenesis data in terms of conformational, entropy and the volume of conformational space accessible to HCDR3 in the, ligand-free state. In the context of autoimmune disease, plasticity of the, ligand-free antibody could provide a mechanism by which anti-DNA, antibodies bind diverse host ligands, and thereby contribute to, pathogenicity.

Anti-DNA antibodies play important roles in the pathogenesis of autoimmune diseases. They also represent a unique and relatively unexplored class of DNA-binding protein. Here, we present a study of conformational changes induced by DNA binding to an anti-ssDNA Fab known as DNA-1. Three crystal structures are reported: a complex of DNA-1 bound to dT3, and two structures of the ligand-free Fab. One of the ligand-free structures was determined from crystals exhibiting perfect hemihedral twinning, and the details of structure determination are provided. Unexpectedly, five residues (H97-H100A) in the apex of heavy chain complementarity-determining region 3 (HCDR3) are disordered in both ligand-free structures. Ligand binding also caused a 2-4A shift of the backbone of Tyr L92 and ordering of the L92 side-chain. In contrast, these residues are highly ordered in the Fab/dT3 complex, where Tyr H100 and Tyr H100A form intimate stacking interactions with DNA bases, and L92 forms the 5' end of the binding site. The structures suggest that HCDR3 is very flexible and adopts multiple conformations in the ligand-free state. These results are discussed in terms of induced fit and pre-existing equilibrium theories of ligand binding. Our results allow new interpretations of existing thermodynamic and mutagenesis data in terms of conformational entropy and the volume of conformational space accessible to HCDR3 in the ligand-free state. In the context of autoimmune disease, plasticity of the ligand-free antibody could provide a mechanism by which anti-DNA antibodies bind diverse host ligands, and thereby contribute to pathogenicity.

==About this Structure==

1XF2 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with SO4 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=1XF2 OCA].

1XF2 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XF2 OCA].

==Reference==

Line 14:

Line 13:

[[Category: Mus musculus]]

[[Category: Protein complex]]

[[Category: Deutscher, S.L.]]

[[Category: Deutscher, S L.]]

[[Category: Prewitt, S.P.]]

[[Category: Prewitt, S P.]]

[[Category: Schuermann, J.P.]]

[[Category: Schuermann, J P.]]

[[Category: Tanner, J.J.]]

[[Category: Tanner, J J.]]

[[Category: SO4]]

[[Category: anti-dna]]

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[[Category: immunoglobulin]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on ~~Sun Nov 18 09~~:44:~~23 2007~~''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:54:05 2008''

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@@ Line 1: / Line 1: @@
-[[Image:1xf2.gif|left|200px]]<br />
+[[Image:1xf2.gif|left|200px]]<br /><applet load="1xf2" size="350" color="white" frame="true" align="right" spinBox="true"
-<applet load="1xf2" size="450" color="white" frame="true" align="right" spinBox="true"
 caption="1xf2, resolution 2.30&Aring;" />
 '''Structure of Fab DNA-1 complexed with dT3'''<br />
 ==Overview==
-Anti-DNA antibodies play important roles in the pathogenesis of autoimmune, diseases. They also represent a unique and relatively unexplored class of, DNA-binding protein. Here, we present a study of conformational changes, induced by DNA binding to an anti-ssDNA Fab known as DNA-1. Three crystal, structures are reported: a complex of DNA-1 bound to dT3, and two, structures of the ligand-free Fab. One of the ligand-free structures was, determined from crystals exhibiting perfect hemihedral twinning, and the, details of structure determination are provided. Unexpectedly, five, residues (H97-H100A) in the apex of heavy chain, complementarity-determining region 3 (HCDR3) are disordered in both, ligand-free structures. Ligand binding also caused a 2-4A shift of the, backbone of Tyr L92 and ordering of the L92 side-chain. In contrast, these, residues are highly ordered in the Fab/dT3 complex, where Tyr H100 and Tyr, H100A form intimate stacking interactions with DNA bases, and L92 forms, the 5' end of the binding site. The structures suggest that HCDR3 is very, flexible and adopts multiple conformations in the ligand-free state. These, results are discussed in terms of induced fit and pre-existing equilibrium, theories of ligand binding. Our results allow new interpretations of, existing thermodynamic and mutagenesis data in terms of conformational, entropy and the volume of conformational space accessible to HCDR3 in the, ligand-free state. In the context of autoimmune disease, plasticity of the, ligand-free antibody could provide a mechanism by which anti-DNA, antibodies bind diverse host ligands, and thereby contribute to, pathogenicity.
+Anti-DNA antibodies play important roles in the pathogenesis of autoimmune diseases. They also represent a unique and relatively unexplored class of DNA-binding protein. Here, we present a study of conformational changes induced by DNA binding to an anti-ssDNA Fab known as DNA-1. Three crystal structures are reported: a complex of DNA-1 bound to dT3, and two structures of the ligand-free Fab. One of the ligand-free structures was determined from crystals exhibiting perfect hemihedral twinning, and the details of structure determination are provided. Unexpectedly, five residues (H97-H100A) in the apex of heavy chain complementarity-determining region 3 (HCDR3) are disordered in both ligand-free structures. Ligand binding also caused a 2-4A shift of the backbone of Tyr L92 and ordering of the L92 side-chain. In contrast, these residues are highly ordered in the Fab/dT3 complex, where Tyr H100 and Tyr H100A form intimate stacking interactions with DNA bases, and L92 forms the 5' end of the binding site. The structures suggest that HCDR3 is very flexible and adopts multiple conformations in the ligand-free state. These results are discussed in terms of induced fit and pre-existing equilibrium theories of ligand binding. Our results allow new interpretations of existing thermodynamic and mutagenesis data in terms of conformational entropy and the volume of conformational space accessible to HCDR3 in the ligand-free state. In the context of autoimmune disease, plasticity of the ligand-free antibody could provide a mechanism by which anti-DNA antibodies bind diverse host ligands, and thereby contribute to pathogenicity.
 ==About this Structure==
-XF2 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with SO4 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1XF2 OCA].
+XF2 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XF2 OCA].
 ==Reference==
@@ Line 14: / Line 13: @@
 [[Category: Mus musculus]]
 [[Category: Protein complex]]
-[[Category: Deutscher, S.L.]]
+[[Category: Deutscher, S L.]]
-[[Category: Prewitt, S.P.]]
+[[Category: Prewitt, S P.]]
-[[Category: Schuermann, J.P.]]
+[[Category: Schuermann, J P.]]
-[[Category: Tanner, J.J.]]
+[[Category: Tanner, J J.]]
 [[Category: SO4]]
 [[Category: anti-dna]]
@@ Line 26: / Line 25: @@
 [[Category: immunoglobulin]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sun Nov 18 09:44:23 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:54:05 2008''