7aal

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(Difference between revisions)

Revision as of 06:53, 8 February 2023

Crystal structure of the F-BAR domain of PSTIPIP1, G258A mutant

Structural highlights

7aal is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

PPIP1_HUMAN Defects in PSTPIP1 are the cause of PAPA syndrome (PAPAS) [MIM:604416; also known as pyogenic sterile arthritis, pyoderma gangrenosum and acne or familial recurrent arthritis (FRA). PAPAS is characterized by autosomal dominant inheritance of early onset, primarily affecting skin and joint tissues. Recurring inflammatory episodes lead to accumulation of sterile, pyogenic, neutrophil-rich material within the affected joints, ultimately resulting in significant destruction.^[1] ^[2]

Function

PPIP1_HUMAN Involved in regulation of the actin cytoskeleton. May regulate the WAS actin-bundling activity. Bridges the interaction between ABL1 and PTPN18 leading to the ABL1 dephosphorylation. May play a role as a scaffold protein between PTPN12 and WAS and allows PTPN12 to dephosphorylate WAS. Has the potential to physically couple CD2 and CD2AP to WAS. Acts downstream of CD2 and CD2AP to recruit WAS to the T-cell:APC contact site so as to promote the actin polymerization required for synapse induction during T-cell activation (By similarity). Down-regulates CD2-stimulated adhesion through the coupling of PTPN12 to CD2.^[3]

Publication Abstract from PubMed

Mutations in the adaptor protein PSTPIP1 cause a spectrum of autoinflammatory diseases, including PAPA and PAMI; however, the mechanism underlying these diseases remains unknown. Most of these mutations lie in PSTPIP1 F-BAR domain, which binds to LYP, a protein tyrosine phosphatase associated with arthritis and lupus. To shed light on the mechanism by which these mutations generate autoinflammatory disorders, we solved the structure of the F-BAR domain of PSTPIP1 alone and bound to the C-terminal homology segment of LYP, revealing a novel mechanism of recognition of Pro-rich motifs by proteins in which a single LYP molecule binds to the PSTPIP1 F-BAR dimer. The residues R228, D246, E250, and E257 of PSTPIP1 that are mutated in immunological diseases directly interact with LYP. These findings link the disruption of the PSTPIP1/LYP interaction to these diseases, and support a critical role for LYP phosphatase in their pathogenesis.

PSTPIP1-LYP phosphatase interaction: structural basis and implications for autoinflammatory disorders.,Manso JA, Marcos T, Ruiz-Martin V, Casas J, Alcon P, Sanchez Crespo M, Bayon Y, de Pereda JM, Alonso A Cell Mol Life Sci. 2022 Feb 12;79(2):131. doi: 10.1007/s00018-022-04173-w. PMID:35152348^[4]

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

References

↑ Shoham NG, Centola M, Mansfield E, Hull KM, Wood G, Wise CA, Kastner DL. Pyrin binds the PSTPIP1/CD2BP1 protein, defining familial Mediterranean fever and PAPA syndrome as disorders in the same pathway. Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13501-6. Epub 2003 Oct 31. PMID:14595024 doi:10.1073/pnas.2135380100
↑ Wise CA, Gillum JD, Seidman CE, Lindor NM, Veile R, Bashiardes S, Lovett M. Mutations in CD2BP1 disrupt binding to PTP PEST and are responsible for PAPA syndrome, an autoinflammatory disorder. Hum Mol Genet. 2002 Apr 15;11(8):961-9. PMID:11971877
↑ Li J, Nishizawa K, An W, Hussey RE, Lialios FE, Salgia R, Sunder-Plassmann R, Reinherz EL. A cdc15-like adaptor protein (CD2BP1) interacts with the CD2 cytoplasmic domain and regulates CD2-triggered adhesion. EMBO J. 1998 Dec 15;17(24):7320-36. PMID:9857189 doi:10.1093/emboj/17.24.7320
↑ Manso JA, Marcos T, Ruiz-Martin V, Casas J, Alcon P, Sanchez Crespo M, Bayon Y, de Pereda JM, Alonso A. PSTPIP1-LYP phosphatase interaction: structural basis and implications for autoinflammatory disorders. Cell Mol Life Sci. 2022 Feb 12;79(2):131. doi: 10.1007/s00018-022-04173-w. PMID:35152348 doi:http://dx.doi.org/10.1007/s00018-022-04173-w

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/7aal"

@@ Line 3: / Line 3: @@
 <StructureSection load='7aal' size='340' side='right'caption='[[7aal]], [[Resolution|resolution]] 1.97&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[7aal]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AAL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AAL FirstGlance]. <br>
+<table><tr><td colspan='2'>[[7aal]] is a 2 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=7AAL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AAL 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;'>[[7aan|7aan]], [[7aam|7aam]]</div></td></tr>
+</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=7aal FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7aal OCA], [https://pdbe.org/7aal PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7aal RCSB], [https://www.ebi.ac.uk/pdbsum/7aal PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7aal ProSAT]</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=7aal FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7aal OCA], [https://pdbe.org/7aal PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7aal RCSB], [https://www.ebi.ac.uk/pdbsum/7aal PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7aal ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[https://www.uniprot.org/uniprot/PPIP1_HUMAN PPIP1_HUMAN]] Defects in PSTPIP1 are the cause of PAPA syndrome (PAPAS) [MIM:[https://omim.org/entry/604416 604416]]; also known as pyogenic sterile arthritis, pyoderma gangrenosum and acne or familial recurrent arthritis (FRA). PAPAS is characterized by autosomal dominant inheritance of early onset, primarily affecting skin and joint tissues. Recurring inflammatory episodes lead to accumulation of sterile, pyogenic, neutrophil-rich material within the affected joints, ultimately resulting in significant destruction.<ref>PMID:14595024</ref> <ref>PMID:11971877</ref>
+[https://www.uniprot.org/uniprot/PPIP1_HUMAN PPIP1_HUMAN] Defects in PSTPIP1 are the cause of PAPA syndrome (PAPAS) [MIM:[https://omim.org/entry/604416 604416]; also known as pyogenic sterile arthritis, pyoderma gangrenosum and acne or familial recurrent arthritis (FRA). PAPAS is characterized by autosomal dominant inheritance of early onset, primarily affecting skin and joint tissues. Recurring inflammatory episodes lead to accumulation of sterile, pyogenic, neutrophil-rich material within the affected joints, ultimately resulting in significant destruction.<ref>PMID:14595024</ref> <ref>PMID:11971877</ref>
 == Function ==
-[[https://www.uniprot.org/uniprot/PPIP1_HUMAN PPIP1_HUMAN]] Involved in regulation of the actin cytoskeleton. May regulate the WAS actin-bundling activity. Bridges the interaction between ABL1 and PTPN18 leading to the ABL1 dephosphorylation. May play a role as a scaffold protein between PTPN12 and WAS and allows PTPN12 to dephosphorylate WAS. Has the potential to physically couple CD2 and CD2AP to WAS. Acts downstream of CD2 and CD2AP to recruit WAS to the T-cell:APC contact site so as to promote the actin polymerization required for synapse induction during T-cell activation (By similarity). Down-regulates CD2-stimulated adhesion through the coupling of PTPN12 to CD2.<ref>PMID:9857189</ref>
+[https://www.uniprot.org/uniprot/PPIP1_HUMAN PPIP1_HUMAN] Involved in regulation of the actin cytoskeleton. May regulate the WAS actin-bundling activity. Bridges the interaction between ABL1 and PTPN18 leading to the ABL1 dephosphorylation. May play a role as a scaffold protein between PTPN12 and WAS and allows PTPN12 to dephosphorylate WAS. Has the potential to physically couple CD2 and CD2AP to WAS. Acts downstream of CD2 and CD2AP to recruit WAS to the T-cell:APC contact site so as to promote the actin polymerization required for synapse induction during T-cell activation (By similarity). Down-regulates CD2-stimulated adhesion through the coupling of PTPN12 to CD2.<ref>PMID:9857189</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 24: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Alcon, P]]
+[[Category: Alcon P]]
-[[Category: Alonso, A]]
+[[Category: Alonso A]]
-[[Category: Bayon, Y]]
+[[Category: Bayon Y]]
-[[Category: Manso, J]]
+[[Category: Manso JA]]
-[[Category: Pereda, J M.de]]
+[[Category: De Pereda JM]]
-[[Category: Inflammatory response]]
-[[Category: Membrane binding]]
-[[Category: Pyogenic arthritis]]
-[[Category: Signaling protein]]

7aal

From Proteopedia

Revision as of 06:53, 8 February 2023

Crystal structure of the F-BAR domain of PSTIPIP1, G258A mutant

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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