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'''Unreleased structure'''


The entry 6mkr is ON HOLD until Paper Publication
==5287 TCR bound to IAb Padi4==
<StructureSection load='6mkr' size='340' side='right'caption='[[6mkr]], [[Resolution|resolution]] 3.35&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6mkr]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MKR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MKR FirstGlance]. <br>
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6mkd|6mkd]]</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein-arginine_deiminase Protein-arginine deiminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.3.15 3.5.3.15] </span></td></tr>
<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=6mkr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mkr OCA], [http://pdbe.org/6mkr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mkr RCSB], [http://www.ebi.ac.uk/pdbsum/6mkr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mkr ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/PADI4_MOUSE PADI4_MOUSE]] Catalyzes the citrullination/deimination of arginine residues of proteins such as histones, thereby playing a key role in histone code and regulation of stem cell maintenance. Citrullinates histone H1 at 'Arg-54' (to form H1R54ci), histone H3 at 'Arg-2', 'Arg-8', 'Arg-17' and/or 'Arg-26' (to form H3R2ci, H3R8ci, H3R17ci, H3R26ci, respectively) and histone H4 at 'Arg-3' (to form H4R3ci). Acts as a key regulator of stem cell maintenance by mediating citrullination of histone H1: citrullination of 'Arg-54' of histone H1 (H1R54ci) results in H1 displacement from chromatin and global chromatin decondensation, thereby promoting pluripotency and stem cell maintenance. Promotes profound chromatin decondensation during the innate immune response to infection in neutrophils by mediating formation of H1R54ci. Citrullination of histone H3 prevents their methylation by CARM1 and HRMT1L2/PRMT1 and represses transcription. Citrullinates EP300/P300 at 'Arg-2142', which favors its interaction with NCOA2/GRIP1.<ref>PMID:15339660</ref> <ref>PMID:20733033</ref> <ref>PMID:23650392</ref> <ref>PMID:24463520</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The neonatal thymus generates Foxp3(+) regulatory T (tTreg) cells that are critical in controlling immune homeostasis and preventing multiorgan autoimmunity. The role of antigen specificity on neonatal tTreg cell selection is unresolved. Here we identify 17 self-peptides recognized by neonatal tTreg cells, and reveal ligand specificity patterns that include self-antigens presented in an age- and inflammation-dependent manner. Fate-mapping studies of neonatal peptidyl arginine deiminase type IV (Padi4)-specific thymocytes reveal disparate fate choices. Neonatal thymocytes expressing T cell receptors that engage IA(b)-Padi4 with moderate dwell times within a conventional docking orientation are exported as tTreg cells. In contrast, Padi4-specific T cell receptors with short dwell times are expressed on CD4(+) T cells, while long dwell times induce negative selection. Temporally, Padi4-specific thymocytes are subject to a developmental stage-specific change in negative selection, which precludes tTreg cell development. Thus, a temporal switch in negative selection and ligand binding kinetics constrains the neonatal tTreg selection window.


Authors: Stadinski, B.D., Blevins, S.J., Huseby, E.S.
A temporal thymic selection switch and ligand binding kinetics constrain neonatal Foxp3(+) Treg cell development.,Stadinski BD, Blevins SJ, Spidale NA, Duke BR, Huseby PG, Stern LJ, Huseby ES Nat Immunol. 2019 Jun 17. pii: 10.1038/s41590-019-0414-1. doi:, 10.1038/s41590-019-0414-1. PMID:31209405<ref>PMID:31209405</ref>


Description: 5287 TCR bound to IAb Padi4
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
[[Category: Huseby, E.S]]
<div class="pdbe-citations 6mkr" style="background-color:#fffaf0;"></div>
[[Category: Stadinski, B.D]]
== References ==
[[Category: Blevins, S.J]]
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Protein-arginine deiminase]]
[[Category: Blevins, S J]]
[[Category: Huseby, E S]]
[[Category: Stadinski, B D]]
[[Category: Immune system]]
[[Category: Major histocompatibility complex]]
[[Category: T cell receptor]]

Revision as of 08:53, 3 July 2019

5287 TCR bound to IAb Padi45287 TCR bound to IAb Padi4

Structural highlights

6mkr is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Activity:Protein-arginine deiminase, with EC number 3.5.3.15
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[PADI4_MOUSE] Catalyzes the citrullination/deimination of arginine residues of proteins such as histones, thereby playing a key role in histone code and regulation of stem cell maintenance. Citrullinates histone H1 at 'Arg-54' (to form H1R54ci), histone H3 at 'Arg-2', 'Arg-8', 'Arg-17' and/or 'Arg-26' (to form H3R2ci, H3R8ci, H3R17ci, H3R26ci, respectively) and histone H4 at 'Arg-3' (to form H4R3ci). Acts as a key regulator of stem cell maintenance by mediating citrullination of histone H1: citrullination of 'Arg-54' of histone H1 (H1R54ci) results in H1 displacement from chromatin and global chromatin decondensation, thereby promoting pluripotency and stem cell maintenance. Promotes profound chromatin decondensation during the innate immune response to infection in neutrophils by mediating formation of H1R54ci. Citrullination of histone H3 prevents their methylation by CARM1 and HRMT1L2/PRMT1 and represses transcription. Citrullinates EP300/P300 at 'Arg-2142', which favors its interaction with NCOA2/GRIP1.[1] [2] [3] [4]

Publication Abstract from PubMed

The neonatal thymus generates Foxp3(+) regulatory T (tTreg) cells that are critical in controlling immune homeostasis and preventing multiorgan autoimmunity. The role of antigen specificity on neonatal tTreg cell selection is unresolved. Here we identify 17 self-peptides recognized by neonatal tTreg cells, and reveal ligand specificity patterns that include self-antigens presented in an age- and inflammation-dependent manner. Fate-mapping studies of neonatal peptidyl arginine deiminase type IV (Padi4)-specific thymocytes reveal disparate fate choices. Neonatal thymocytes expressing T cell receptors that engage IA(b)-Padi4 with moderate dwell times within a conventional docking orientation are exported as tTreg cells. In contrast, Padi4-specific T cell receptors with short dwell times are expressed on CD4(+) T cells, while long dwell times induce negative selection. Temporally, Padi4-specific thymocytes are subject to a developmental stage-specific change in negative selection, which precludes tTreg cell development. Thus, a temporal switch in negative selection and ligand binding kinetics constrains the neonatal tTreg selection window.

A temporal thymic selection switch and ligand binding kinetics constrain neonatal Foxp3(+) Treg cell development.,Stadinski BD, Blevins SJ, Spidale NA, Duke BR, Huseby PG, Stern LJ, Huseby ES Nat Immunol. 2019 Jun 17. pii: 10.1038/s41590-019-0414-1. doi:, 10.1038/s41590-019-0414-1. PMID:31209405[5]

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

References

  1. ↑ Cuthbert GL, Daujat S, Snowden AW, Erdjument-Bromage H, Hagiwara T, Yamada M, Schneider R, Gregory PD, Tempst P, Bannister AJ, Kouzarides T. Histone deimination antagonizes arginine methylation. Cell. 2004 Sep 3;118(5):545-53. PMID:15339660 doi:10.1016/j.cell.2004.08.020
  2. ↑ Li P, Li M, Lindberg MR, Kennett MJ, Xiong N, Wang Y. PAD4 is essential for antibacterial innate immunity mediated by neutrophil extracellular traps. J Exp Med. 2010 Aug 30;207(9):1853-62. doi: 10.1084/jem.20100239. Epub 2010 Aug, 23. PMID:20733033 doi:http://dx.doi.org/10.1084/jem.20100239
  3. ↑ Martinod K, Demers M, Fuchs TA, Wong SL, Brill A, Gallant M, Hu J, Wang Y, Wagner DD. Neutrophil histone modification by peptidylarginine deiminase 4 is critical for deep vein thrombosis in mice. Proc Natl Acad Sci U S A. 2013 May 21;110(21):8674-9. doi:, 10.1073/pnas.1301059110. Epub 2013 May 6. PMID:23650392 doi:http://dx.doi.org/10.1073/pnas.1301059110
  4. ↑ Christophorou MA, Castelo-Branco G, Halley-Stott RP, Oliveira CS, Loos R, Radzisheuskaya A, Mowen KA, Bertone P, Silva JC, Zernicka-Goetz M, Nielsen ML, Gurdon JB, Kouzarides T. Citrullination regulates pluripotency and histone H1 binding to chromatin. Nature. 2014 Mar 6;507(7490):104-8. doi: 10.1038/nature12942. Epub 2014 Jan 26. PMID:24463520 doi:http://dx.doi.org/10.1038/nature12942
  5. ↑ Stadinski BD, Blevins SJ, Spidale NA, Duke BR, Huseby PG, Stern LJ, Huseby ES. A temporal thymic selection switch and ligand binding kinetics constrain neonatal Foxp3(+) Treg cell development. Nat Immunol. 2019 Jun 17. pii: 10.1038/s41590-019-0414-1. doi:, 10.1038/s41590-019-0414-1. PMID:31209405 doi:http://dx.doi.org/10.1038/s41590-019-0414-1

6mkr, resolution 3.35Å

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