3rzu

From Proteopedia

(Difference between revisions)

Revision as of 10:32, 22 June 2022

The Crystal Structure of the Catalytic Domain of AMSH

Structural highlights

3rzu is a 7 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	2znr, 3rzv
Gene:	AMSH, STAMBP, STAMBP (AMSH) (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[STABP_HUMAN] Microcephaly-capillary malformation syndrome. The disease is caused by mutations affecting the gene represented in this entry.

Function

[STABP_HUMAN] Zinc metalloprotease that specifically cleaves 'Lys-63'-linked polyubiquitin chains. Does not cleave 'Lys-48'-linked polyubiquitin chains (By similarity). Plays a role in signal transduction for cell growth and MYC induction mediated by IL-2 and GM-CSF. Potentiates BMP (bone morphogenetic protein) signaling by antagonizing the inhibitory action of SMAD6 and SMAD7. Has a key role in regulation of cell surface receptor-mediated endocytosis and ubiquitin-dependent sorting of receptors to lysosomes. Endosomal localization of STAMBP is required for efficient EGFR degradation but not for its internalization (By similarity). Involved in the negative regulation of PI3K-AKT-mTOR and RAS-MAP signaling pathways.^[1] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

AMSH plays a critical role in the ESCRT (endosomal sorting complexes required for transport) machinery, which facilitates the down-regulation and degradation of cell-surface receptors. It displays a high level of specificity toward cleavage of Lys63-linked polyubiquitin chains, the structural basis of which has been understood recently through the crystal structure of a highly related, but ESCRT-independent, protein AMSH-LP (AMSH-like protein). We have determined the X-ray structure of two constructs representing the catalytic domain of AMSH: AMSH244, the JAMM (JAB1/MPN/MOV34)-domain-containing polypeptide segment from residues 244 to 424, and AMSH219(E280A), an active-site mutant, Glu280 to Ala, of the segment from 219 to 424. In addition to confirming the expected zinc coordination in the protein, the structures reveal that the catalytic domains of AMSH and AMSH-LP are nearly identical; however, guanidine-hydrochloride-induced unfolding studies show that the catalytic domain of AMSH is thermodynamically less stable than that of AMSH-LP, indicating that the former is perhaps structurally more plastic. Much to our surprise, in the AMSH219(E280A) structure, the catalytic zinc was still held in place, by the compensatory effect of an aspartate from a nearby loop moving into a position where it could coordinate with the zinc, once again suggesting the plasticity of AMSH. Additionally, a model of AMSH244 bound to Lys63-linked diubiquitin reveals a type of interface for the distal ubiquitin significantly different from that seen in AMSH-LP. Altogether, we believe that our data provide important insight into the structural difference between the two proteins that may translate into the difference in their biological function.

Structural and Thermodynamic Comparison of the Catalytic Domain of AMSH and AMSH-LP: Nearly Identical Fold but Different Stability.,Davies CW, Paul LN, Kim MI, Das C J Mol Biol. 2011 Oct 21;413(2):416-29. Epub 2011 Aug 24. PMID:21888914^[6]

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

References

↑ Tanaka N, Kaneko K, Asao H, Kasai H, Endo Y, Fujita T, Takeshita T, Sugamura K. Possible involvement of a novel STAM-associated molecule "AMSH" in intracellular signal transduction mediated by cytokines. J Biol Chem. 1999 Jul 2;274(27):19129-35. PMID:10383417
↑ Itoh F, Asao H, Sugamura K, Heldin CH, ten Dijke P, Itoh S. Promoting bone morphogenetic protein signaling through negative regulation of inhibitory Smads. EMBO J. 2001 Aug 1;20(15):4132-42. PMID:11483516 doi:http://dx.doi.org/10.1093/emboj/20.15.4132
↑ McCullough J, Clague MJ, Urbe S. AMSH is an endosome-associated ubiquitin isopeptidase. J Cell Biol. 2004 Aug 16;166(4):487-92. PMID:15314065 doi:http://dx.doi.org/10.1083/jcb.200401141
↑ Ma YM, Boucrot E, Villen J, Affar el B, Gygi SP, Gottlinger HG, Kirchhausen T. Targeting of AMSH to endosomes is required for epidermal growth factor receptor degradation. J Biol Chem. 2007 Mar 30;282(13):9805-12. Epub 2007 Jan 29. PMID:17261583 doi:http://dx.doi.org/10.1074/jbc.M611635200
↑ McDonell LM, Mirzaa GM, Alcantara D, Schwartzentruber J, Carter MT, Lee LJ, Clericuzio CL, Graham JM Jr, Morris-Rosendahl DJ, Polster T, Acsadi G, Townshend S, Williams S, Halbert A, Isidor B, David A, Smyser CD, Paciorkowski AR, Willing M, Woulfe J, Das S, Beaulieu CL, Marcadier J, Geraghty MT, Frey BJ, Majewski J, Bulman DE, Dobyns WB, O'Driscoll M, Boycott KM. Mutations in STAMBP, encoding a deubiquitinating enzyme, cause microcephaly-capillary malformation syndrome. Nat Genet. 2013 May;45(5):556-62. doi: 10.1038/ng.2602. Epub 2013 Mar 31. PMID:23542699 doi:http://dx.doi.org/10.1038/ng.2602
↑ Davies CW, Paul LN, Kim MI, Das C. Structural and Thermodynamic Comparison of the Catalytic Domain of AMSH and AMSH-LP: Nearly Identical Fold but Different Stability. J Mol Biol. 2011 Oct 21;413(2):416-29. Epub 2011 Aug 24. PMID:21888914 doi:10.1016/j.jmb.2011.08.029

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/3rzu"

@@ Line 1: / Line 1: @@
 ==The Crystal Structure of the Catalytic Domain of AMSH==
-<StructureSection load='3rzu' size='340' side='right' caption='[[3rzu]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
+<StructureSection load='3rzu' size='340' side='right'caption='[[3rzu]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3rzu]] is a 7 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=3RZU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3RZU FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3rzu]] is a 7 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=3RZU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3RZU FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2znr|2znr]], [[3rzv|3rzv]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2znr|2znr]], [[3rzv|3rzv]]</div></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AMSH, STAMBP, STAMBP (AMSH) ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AMSH, STAMBP, STAMBP (AMSH) ([https://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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3rzu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rzu OCA], [http://pdbe.org/3rzu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3rzu RCSB], [http://www.ebi.ac.uk/pdbsum/3rzu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3rzu 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=3rzu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rzu OCA], [https://pdbe.org/3rzu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3rzu RCSB], [https://www.ebi.ac.uk/pdbsum/3rzu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3rzu ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/STABP_HUMAN STABP_HUMAN]] Microcephaly-capillary malformation syndrome. The disease is caused by mutations affecting the gene represented in this entry.
+[[https://www.uniprot.org/uniprot/STABP_HUMAN STABP_HUMAN]] Microcephaly-capillary malformation syndrome. The disease is caused by mutations affecting the gene represented in this entry.
 == Function ==
-[[http://www.uniprot.org/uniprot/STABP_HUMAN STABP_HUMAN]] Zinc metalloprotease that specifically cleaves 'Lys-63'-linked polyubiquitin chains. Does not cleave 'Lys-48'-linked polyubiquitin chains (By similarity). Plays a role in signal transduction for cell growth and MYC induction mediated by IL-2 and GM-CSF. Potentiates BMP (bone morphogenetic protein) signaling by antagonizing the inhibitory action of SMAD6 and SMAD7. Has a key role in regulation of cell surface receptor-mediated endocytosis and ubiquitin-dependent sorting of receptors to lysosomes. Endosomal localization of STAMBP is required for efficient EGFR degradation but not for its internalization (By similarity). Involved in the negative regulation of PI3K-AKT-mTOR and RAS-MAP signaling pathways.<ref>PMID:10383417</ref> <ref>PMID:11483516</ref> <ref>PMID:15314065</ref> <ref>PMID:17261583</ref> <ref>PMID:23542699</ref>
+[[https://www.uniprot.org/uniprot/STABP_HUMAN STABP_HUMAN]] Zinc metalloprotease that specifically cleaves 'Lys-63'-linked polyubiquitin chains. Does not cleave 'Lys-48'-linked polyubiquitin chains (By similarity). Plays a role in signal transduction for cell growth and MYC induction mediated by IL-2 and GM-CSF. Potentiates BMP (bone morphogenetic protein) signaling by antagonizing the inhibitory action of SMAD6 and SMAD7. Has a key role in regulation of cell surface receptor-mediated endocytosis and ubiquitin-dependent sorting of receptors to lysosomes. Endosomal localization of STAMBP is required for efficient EGFR degradation but not for its internalization (By similarity). Involved in the negative regulation of PI3K-AKT-mTOR and RAS-MAP signaling pathways.<ref>PMID:10383417</ref> <ref>PMID:11483516</ref> <ref>PMID:15314065</ref> <ref>PMID:17261583</ref> <ref>PMID:23542699</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 27: / Line 27: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Das, C]]
 [[Category: Davies, C W]]

3rzu

From Proteopedia

Revision as of 10:32, 22 June 2022

The Crystal Structure of the Catalytic Domain of AMSH

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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