6v7q

From Proteopedia

(Difference between revisions)

Revision as of 07:36, 27 May 2020

Crystal structure of SUMO1 in complex with phosphorylated PIAS-SIM2

Structural highlights

6v7q is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:
Related:	6v7p
Gene:	SUMO1, SMT3C, SMT3H3, UBL1, OK/SW-cl.43 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[SUMO1_HUMAN] Defects in SUMO1 are the cause of non-syndromic orofacial cleft type 10 (OFC10) [MIM:613705]; also called non-syndromic cleft lip with or without cleft palate 10. OFC10 is a birth defect consisting of cleft lips with or without cleft palate. Cleft lips are associated with cleft palate in two-third of cases. A cleft lip can occur on one or both sides and range in severity from a simple notch in the upper lip to a complete opening in the lip extending into the floor of the nostril and involving the upper gum. Note=A chromosomal aberation involving SUMO1 is the cause of OFC10. Translocation t(2;8)(q33.1;q24.3). The breakpoint occurred in the SUMO1 gene and resulted in haploinsufficiency confirmed by protein assays.^[1]

Function

[SUMO1_HUMAN] Ubiquitin-like protein that can be covalently attached to proteins as a monomer or a lysine-linked polymer. Covalent attachment via an isopeptide bond to its substrates requires prior activation by the E1 complex SAE1-SAE2 and linkage to the E2 enzyme UBE2I, and can be promoted by E3 ligases such as PIAS1-4, RANBP2 or CBX4. This post-translational modification on lysine residues of proteins plays a crucial role in a number of cellular processes such as nuclear transport, DNA replication and repair, mitosis and signal transduction. Involved for instance in targeting RANGAP1 to the nuclear pore complex protein RANBP2. Polymeric SUMO1 chains are also susceptible to polyubiquitination which functions as a signal for proteasomal degradation of modified proteins. May also regulate a network of genes involved in palate development.^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

The human PIAS proteins are small ubiquitin-like modifier (SUMO) E3 ligases that participate in important cellular functions. Several of these functions depend on a conserved SUMO-interacting motif (SIM) located in the central region of all PIAS proteins (SIM1). Recently, it was determined that Siz2, a yeast homolog of PIAS proteins, possesses a second SIM at its C terminus (SIM2). Sequence alignment indicates that a SIM2 is also present in PIAS1-3, but not PIAS4. Using biochemical and structural studies, we demonstrate PIAS-SIM2 binds to SUMO1, but that phosphorylation of the PIAS-SIM2 or acetylation of SUMO1 alter this interaction in a manner distinct from what is observed for the PIAS-SIM1. We also show that the PIAS-SIM2 plays a key role in formation of a UBC9-PIAS1-SUMO1 complex. These results provide insights into how post-translational modifications selectively regulate the specificity of multiple SIMs found in the PIAS proteins by exploiting the plasticity built into the SUMO-SIM binding interface.

Characterization of a C-Terminal SUMO-Interacting Motif Present in Select PIAS-Family Proteins.,Lussier-Price M, Mascle XH, Cappadocia L, Kamada R, Sakaguchi K, Wahba HM, Omichinski JG Structure. 2020 May 5;28(5):573-585.e5. doi: 10.1016/j.str.2020.04.002. Epub 2020, Apr 28. PMID:32348746^[6]

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

References

↑ Alkuraya FS, Saadi I, Lund JJ, Turbe-Doan A, Morton CC, Maas RL. SUMO1 haploinsufficiency leads to cleft lip and palate. Science. 2006 Sep 22;313(5794):1751. PMID:16990542 doi:10.1126/science.1128406
↑ Mahajan R, Delphin C, Guan T, Gerace L, Melchior F. A small ubiquitin-related polypeptide involved in targeting RanGAP1 to nuclear pore complex protein RanBP2. Cell. 1997 Jan 10;88(1):97-107. PMID:9019411
↑ Kamitani T, Nguyen HP, Yeh ET. Preferential modification of nuclear proteins by a novel ubiquitin-like molecule. J Biol Chem. 1997 May 30;272(22):14001-4. PMID:9162015
↑ Meulmeester E, Kunze M, Hsiao HH, Urlaub H, Melchior F. Mechanism and consequences for paralog-specific sumoylation of ubiquitin-specific protease 25. Mol Cell. 2008 Jun 6;30(5):610-9. doi: 10.1016/j.molcel.2008.03.021. PMID:18538659 doi:10.1016/j.molcel.2008.03.021
↑ Tatham MH, Geoffroy MC, Shen L, Plechanovova A, Hattersley N, Jaffray EG, Palvimo JJ, Hay RT. RNF4 is a poly-SUMO-specific E3 ubiquitin ligase required for arsenic-induced PML degradation. Nat Cell Biol. 2008 May;10(5):538-46. doi: 10.1038/ncb1716. Epub 2008 Apr 13. PMID:18408734 doi:10.1038/ncb1716
↑ Lussier-Price M, Mascle XH, Cappadocia L, Kamada R, Sakaguchi K, Wahba HM, Omichinski JG. Characterization of a C-Terminal SUMO-Interacting Motif Present in Select PIAS-Family Proteins. Structure. 2020 May 5;28(5):573-585.e5. doi: 10.1016/j.str.2020.04.002. Epub 2020, Apr 28. PMID:32348746 doi:http://dx.doi.org/10.1016/j.str.2020.04.002

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/6v7q"

@@ Line 3: / Line 3: @@
 <StructureSection load='6v7q' size='340' side='right'caption='[[6v7q]], [[Resolution|resolution]] 1.35&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6v7q]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6V7Q OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6V7Q FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6v7q]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6V7Q OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6V7Q FirstGlance]. <br>
 </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6v7p|6v7p]]</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=6v7q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v7q OCA], [http://pdbe.org/6v7q PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6v7q RCSB], [http://www.ebi.ac.uk/pdbsum/6v7q PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6v7q ProSAT]</span></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SUMO1, SMT3C, SMT3H3, UBL1, OK/SW-cl.43 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6v7q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v7q OCA], [http://pdbe.org/6v7q PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6v7q RCSB], [http://www.ebi.ac.uk/pdbsum/6v7q PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6v7q ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 12: / Line 13: @@
 == Function ==
 [[http://www.uniprot.org/uniprot/SUMO1_HUMAN SUMO1_HUMAN]] Ubiquitin-like protein that can be covalently attached to proteins as a monomer or a lysine-linked polymer. Covalent attachment via an isopeptide bond to its substrates requires prior activation by the E1 complex SAE1-SAE2 and linkage to the E2 enzyme UBE2I, and can be promoted by E3 ligases such as PIAS1-4, RANBP2 or CBX4. This post-translational modification on lysine residues of proteins plays a crucial role in a number of cellular processes such as nuclear transport, DNA replication and repair, mitosis and signal transduction. Involved for instance in targeting RANGAP1 to the nuclear pore complex protein RANBP2. Polymeric SUMO1 chains are also susceptible to polyubiquitination which functions as a signal for proteasomal degradation of modified proteins. May also regulate a network of genes involved in palate development.<ref>PMID:9019411</ref> <ref>PMID:9162015</ref> <ref>PMID:18538659</ref> <ref>PMID:18408734</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The human PIAS proteins are small ubiquitin-like modifier (SUMO) E3 ligases that participate in important cellular functions. Several of these functions depend on a conserved SUMO-interacting motif (SIM) located in the central region of all PIAS proteins (SIM1). Recently, it was determined that Siz2, a yeast homolog of PIAS proteins, possesses a second SIM at its C terminus (SIM2). Sequence alignment indicates that a SIM2 is also present in PIAS1-3, but not PIAS4. Using biochemical and structural studies, we demonstrate PIAS-SIM2 binds to SUMO1, but that phosphorylation of the PIAS-SIM2 or acetylation of SUMO1 alter this interaction in a manner distinct from what is observed for the PIAS-SIM1. We also show that the PIAS-SIM2 plays a key role in formation of a UBC9-PIAS1-SUMO1 complex. These results provide insights into how post-translational modifications selectively regulate the specificity of multiple SIMs found in the PIAS proteins by exploiting the plasticity built into the SUMO-SIM binding interface.
+Characterization of a C-Terminal SUMO-Interacting Motif Present in Select PIAS-Family Proteins.,Lussier-Price M, Mascle XH, Cappadocia L, Kamada R, Sakaguchi K, Wahba HM, Omichinski JG Structure. 2020 May 5;28(5):573-585.e5. doi: 10.1016/j.str.2020.04.002. Epub 2020, Apr 28. PMID:32348746<ref>PMID:32348746</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 6v7q" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Large Structures]]
 [[Category: Cappadocia, L]]

6v7q

From Proteopedia

Revision as of 07:36, 27 May 2020

Crystal structure of SUMO1 in complex with phosphorylated PIAS-SIM2

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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