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3pnw

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Revision as of 17:59, 25 December 2014

Crystal Structure of the tudor domain of human TDRD3 in complex with an anti-TDRD3 FAB

Structural highlights

3pnw is a 24 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	TDRD3 (Homo sapiens)
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[TDRD3_HUMAN] Scaffolding protein that specifically recognizes and binds dimethylarginine-containing proteins. In nucleus, acts as a coactivator: recognizes and binds asymmetric dimethylation on the core histone tails associated with transcriptional activation (H3R17me2a and H4R3me2a) and recruits proteins at these arginine-methylated loci. In cytoplasm, may play a role in the assembly and/or disassembly of mRNA stress granules and in the regulation of translation of target mRNAs by binding Arg/Gly-rich motifs (GAR) in dimethylarginine-containing proteins.^[1] ^[2] ^[3]

Publication Abstract from PubMed

A synthetic phage-displayed antibody repertoire was constructed with equivalent chemical diversity in the third complementarity-determining regions of the heavy (CDR-H3) and light (CDR-L3) chains, which contrasts with natural antibodies in which CDR-H3 is much more diverse than CDR-L3 due to the genetic mechanisms that generate antibody encoding genes. Surprisingly, the synthetic repertoire yielded numerous functional antibodies that contained mutated CDR-L3 sequences but a fixed CDR-H3 sequence. Alanine-scanning analysis of antibodies that recognized 10 different antigens but contained a common CDR-H3 loop showed that, in most cases, the fixed CDR-H3 sequence was able to contribute favorably to antigen recognition, but in some cases, the loop was functionally inert. Structural analysis of one such antibody in complex with antigen showed that the inert CDR-H3 loop was nonetheless highly buried at the antibody-antigen interface. Taken together, these results show that CDR-H3 diversity is not necessarily required for the generation of antibodies that recognize diverse protein antigens with high affinity and specificity, and if given the chance, CDR-L3 readily assumes the dominant role for antigen recognition. These results contrast with the commonly accepted view of antigen recognition derived from the analysis of natural antibodies, in which CDR-H3 is presumed to be dominant and CDR-L3 is presumed to play an auxiliary role. Furthermore, the results show that natural antibody function is genetically constrained, and it should be possible to develop more functional synthetic antibody libraries by expanding the diversity of CDR-L3 beyond what is observed in nature.

CDR-H3 Diversity Is Not Required for Antigen Recognition by Synthetic Antibodies.,Persson H, Ye W, Wernimont A, Adams JJ, Lam R, Sidhu SS J Mol Biol. 2012 Dec 3. pii: S0022-2836(12)00909-6. doi:, 10.1016/j.jmb.2012.11.037. PMID:23219464^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Goulet I, Boisvenue S, Mokas S, Mazroui R, Cote J. TDRD3, a novel Tudor domain-containing protein, localizes to cytoplasmic stress granules. Hum Mol Genet. 2008 Oct 1;17(19):3055-74. doi: 10.1093/hmg/ddn203. Epub 2008 Jul , 15. PMID:18632687 doi:10.1093/hmg/ddn203
↑ Cote J, Richard S. Tudor domains bind symmetrical dimethylated arginines. J Biol Chem. 2005 Aug 5;280(31):28476-83. Epub 2005 Jun 6. PMID:15955813 doi:M414328200
↑ Yang Y, Lu Y, Espejo A, Wu J, Xu W, Liang S, Bedford MT. TDRD3 is an effector molecule for arginine-methylated histone marks. Mol Cell. 2010 Dec 22;40(6):1016-23. doi: 10.1016/j.molcel.2010.11.024. PMID:21172665 doi:10.1016/j.molcel.2010.11.024
↑ Persson H, Ye W, Wernimont A, Adams JJ, Lam R, Sidhu SS. CDR-H3 Diversity Is Not Required for Antigen Recognition by Synthetic Antibodies. J Mol Biol. 2012 Dec 3. pii: S0022-2836(12)00909-6. doi:, 10.1016/j.jmb.2012.11.037. PMID:23219464 doi:10.1016/j.jmb.2012.11.037

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3pnw"

@@ Line 7: / Line 7: @@
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3pnw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3pnw OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3pnw RCSB], [http://www.ebi.ac.uk/pdbsum/3pnw PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/TDRD3_HUMAN TDRD3_HUMAN]] Scaffolding protein that specifically recognizes and binds dimethylarginine-containing proteins. In nucleus, acts as a coactivator: recognizes and binds asymmetric dimethylation on the core histone tails associated with transcriptional activation (H3R17me2a and H4R3me2a) and recruits proteins at these arginine-methylated loci. In cytoplasm, may play a role in the assembly and/or disassembly of mRNA stress granules and in the regulation of translation of target mRNAs by binding Arg/Gly-rich motifs (GAR) in dimethylarginine-containing proteins.<ref>PMID:18632687</ref> <ref>PMID:15955813</ref> <ref>PMID:21172665</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

3pnw

From Proteopedia

Revision as of 17:59, 25 December 2014

Crystal Structure of the tudor domain of human TDRD3 in complex with an anti-TDRD3 FAB

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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