3apm

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of the human SNP PAD4 protein

Structural highlights

3apm is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.5Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

PADI4_HUMAN Genetic variations in PADI4 are a cause of susceptibility to rheumatoid arthritis (RA) [MIM:180300. It is a systemic inflammatory disease with autoimmune features and a complex genetic component. It primarily affects the joints and is characterized by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Note=Could have an important role in the pathogenesis of rheumatoid arthritis by increasing citrullination of proteins in rheumatoid arthritis synovial tissues, leading, in a cytokine-rich milieu, to a break in tolerance to citrullinated peptides processed and presented in the appropriate HLA context.^[1]

Function

PADI4_HUMAN Catalyzes the citrullination/deimination of arginine residues of proteins. Citrullinates histone H3 at 'Arg-8' and/or 'Arg-17' and histone H4 at 'Arg-3', which prevents their methylation by CARM1 and HRMT1L2/PRMT1 and represses transcription. Citrullinates EP300/P300 at 'Arg-2142', which favors its interaction with NCOA2/GRIP1.^[2] ^[3]

Publication Abstract from PubMed

PAD4 is a peptidylarginine deiminase that catalyzes citrullination, a type of post-translational modification. In this reaction, arginine residues in proteins are converted to citrulline. PAD4 promotes the deimination of arginine residues in histones and may regulate transcription in the context of the chromatin. Single-nucleotide polymorphisms (SNP) in the gene encoding PAD4 identified it as one of the genes associated with susceptibility to rheumatoid arthritis. The PAD4 SNP involve three amino-acid substitutions: Ser55 to Gly, Ala82 to Val and Ala112 to Gly. Autoantibodies for improperly citrullinated proteins have been found in rheumatoid arthritis patients, suggesting that the PAD4(SNP) mRNA is more stable than the conventional PAD4 mRNA and/or the PAD4(SNP) protein possesses a higher citrullination activity than the PAD4 protein. In order to study the effects of the three amino-acid substitutions found in PAD4(SNP), the crystal structure of PAD4(SNP) was determined and it was found that the amino-acid substitutions in PAD4(SNP) only induced conformational changes within the N-terminal domain, not in the active centre for citrullination located in the C-terminal domain. Biochemical analyses also suggested that the citrullination activity of PAD4(SNP) may not substantially differ from that of conventional PAD4. These structural and biochemical findings suggested that the improper protein citrullination found in rheumatoid arthritis patients is not caused by defects in the citrullination activity of PAD4(SNP) but by other reasons such as enhanced PAD4(SNP) mRNA stability.

Structural and biochemical analyses of the human PAD4 variant encoded by a functional haplotype gene.,Horikoshi N, Tachiwana H, Saito K, Osakabe A, Sato M, Yamada M, Akashi S, Nishimura Y, Kagawa W, Kurumizaka H Acta Crystallogr D Biol Crystallogr. 2011 Feb;67(Pt 2):112-8. Epub 2011, Jan 8. PMID:21245532^[4]

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

References

↑ Suzuki A, Yamada R, Chang X, Tokuhiro S, Sawada T, Suzuki M, Nagasaki M, Nakayama-Hamada M, Kawaida R, Ono M, Ohtsuki M, Furukawa H, Yoshino S, Yukioka M, Tohma S, Matsubara T, Wakitani S, Teshima R, Nishioka Y, Sekine A, Iida A, Takahashi A, Tsunoda T, Nakamura Y, Yamamoto K. Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis. Nat Genet. 2003 Aug;34(4):395-402. PMID:12833157 doi:10.1038/ng1206
↑ 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
↑ Wang Y, Wysocka J, Sayegh J, Lee YH, Perlin JR, Leonelli L, Sonbuchner LS, McDonald CH, Cook RG, Dou Y, Roeder RG, Clarke S, Stallcup MR, Allis CD, Coonrod SA. Human PAD4 regulates histone arginine methylation levels via demethylimination. Science. 2004 Oct 8;306(5694):279-83. Epub 2004 Sep 2. PMID:15345777 doi:10.1126/science.1101400
↑ Horikoshi N, Tachiwana H, Saito K, Osakabe A, Sato M, Yamada M, Akashi S, Nishimura Y, Kagawa W, Kurumizaka H. Structural and biochemical analyses of the human PAD4 variant encoded by a functional haplotype gene. Acta Crystallogr D Biol Crystallogr. 2011 Feb;67(Pt 2):112-8. Epub 2011, Jan 8. PMID:21245532 doi:10.1107/S0907444910051711

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

@@ Line 3: / Line 3: @@
 <StructureSection load='3apm' size='340' side='right'caption='[[3apm]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3apm]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3APM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3APM FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3apm]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3APM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3APM FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3apn|3apn]]</div></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PADI4, PADI5, PDI5 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Protein-arginine_deiminase Protein-arginine deiminase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=3apm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3apm OCA], [https://pdbe.org/3apm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3apm RCSB], [https://www.ebi.ac.uk/pdbsum/3apm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3apm ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[https://www.uniprot.org/uniprot/PADI4_HUMAN PADI4_HUMAN]] Genetic variations in PADI4 are a cause of susceptibility to rheumatoid arthritis (RA) [MIM:[https://omim.org/entry/180300 180300]]. It is a systemic inflammatory disease with autoimmune features and a complex genetic component. It primarily affects the joints and is characterized by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Note=Could have an important role in the pathogenesis of rheumatoid arthritis by increasing citrullination of proteins in rheumatoid arthritis synovial tissues, leading, in a cytokine-rich milieu, to a break in tolerance to citrullinated peptides processed and presented in the appropriate HLA context.<ref>PMID:12833157</ref>
+[https://www.uniprot.org/uniprot/PADI4_HUMAN PADI4_HUMAN] Genetic variations in PADI4 are a cause of susceptibility to rheumatoid arthritis (RA) [MIM:[https://omim.org/entry/180300 180300]. It is a systemic inflammatory disease with autoimmune features and a complex genetic component. It primarily affects the joints and is characterized by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Note=Could have an important role in the pathogenesis of rheumatoid arthritis by increasing citrullination of proteins in rheumatoid arthritis synovial tissues, leading, in a cytokine-rich milieu, to a break in tolerance to citrullinated peptides processed and presented in the appropriate HLA context.<ref>PMID:12833157</ref>
 == Function ==
-[[https://www.uniprot.org/uniprot/PADI4_HUMAN PADI4_HUMAN]] Catalyzes the citrullination/deimination of arginine residues of proteins. Citrullinates histone H3 at 'Arg-8' and/or 'Arg-17' and histone H4 at 'Arg-3', which 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:15345777</ref>
+[https://www.uniprot.org/uniprot/PADI4_HUMAN PADI4_HUMAN] Catalyzes the citrullination/deimination of arginine residues of proteins. Citrullinates histone H3 at 'Arg-8' and/or 'Arg-17' and histone H4 at 'Arg-3', which 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:15345777</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 26: / Line 24: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Protein-arginine deiminase]]
+[[Category: Akashi S]]
-[[Category: Akashi, S]]
+[[Category: Horikoshi N]]
-[[Category: Horikoshi, N]]
+[[Category: Kagawa W]]
-[[Category: Kagawa, W]]
+[[Category: Kurumizaka H]]
-[[Category: Kurumizaka, H]]
+[[Category: Nishimura Y]]
-[[Category: Nishimura, Y]]
+[[Category: Osakabe A]]
-[[Category: Osakabe, A]]
+[[Category: Saito K]]
-[[Category: Saito, K]]
+[[Category: Sato M]]
-[[Category: Sato, M]]
+[[Category: Tachiwana H]]
-[[Category: Tachiwana, H]]
+[[Category: Yamada M]]
-[[Category: Yamada, M]]
-[[Category: Alpha/beta-propeller]]
-[[Category: Arginine citrullination]]
-[[Category: Benzoyl-l-arginine amide binding]]
-[[Category: Calcium binding]]
-[[Category: Histone binding]]
-[[Category: Hydrolase]]
-[[Category: Immunoglobulin-like]]
-[[Category: Nucleus]]
-[[Category: Post-translational modification]]

3apm

From Proteopedia

Current revision

Crystal structure of the human SNP PAD4 protein

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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