6tzc

From Proteopedia

(Difference between revisions)

Revision as of 15:39, 20 November 2019

Crystal Structure of African Swine Fever Virus A179L with the Autophagy Regulator Beclin

Structural highlights

6tzc is a 3 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[MALE_ECOLI] Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides. [BECN1_PIG] Plays a central role in autophagy. Acts as core subunit of the PI3K complex that mediates formation of phosphatidylinositol 3-phosphate; different complex forms are believed to play a role in multiple membrane trafficking pathways: PI3KC3-C1 is involved in initiation of autophagosomes and PI3KC3-C2 in maturation of autophagosomes and endocytosis. Involved in regulation of degradative endocytic trafficking and required for the abcission step in cytokinesis, probably in the context of PI3KC3-C2. Essential for the formation of PI3KC3-C2 but not PI3KC3-C1 PI3K complex forms. Involved in endocytosis. May play a role in antiviral host defense (By similarity).[UniProtKB:O88597][UniProtKB:Q14457][UniProtKB:Q91XJ1] Beclin-1-C 35 kDa localized to mitochondria can promote apoptosis; it induces the mitochondrial translocation of BAX and the release of proapoptotic factors.[UniProtKB:O88597][UniProtKB:Q14457] [ARBH_ASFB7] Suppresses apoptosis in host cell and thus facilitates production of progeny virions (PubMed:9123849, PubMed:18329683). Has the ability to potentially bind to all the members of the proapoptotic Bcl-2 family (PubMed:28053104, PubMed:18329683).^[1] ^[2] ^[3]

Publication Abstract from PubMed

Subversion of programmed cell death-based host defence systems is a prominent feature of infections by large DNA viruses. African swine fever virus (ASFV) is a large DNA virus and sole member of the Asfarviridae family that harbours the B-cell lymphoma 2 or Bcl-2 homolog A179L. A179L has been shown to bind to a range of cell death-inducing host proteins, including pro-apoptotic Bcl-2 proteins as well as the autophagy regulator Beclin. Here we report the crystal structure of A179L bound to the Beclin BH3 motif. A179L engages Beclin using the same canonical ligand-binding groove that is utilized to bind to pro-apoptotic Bcl-2 proteins. The mode of binding of Beclin to A179L mirrors that of Beclin binding to human Bcl-2 and Bcl-xL as well as murine gamma-herpesvirus 68. The introduction of bulky hydrophobic residues into the A179L ligand-binding groove via site-directed mutagenesis ablates binding of Beclin to A179L, leading to a loss of the ability of A179L to modulate autophagosome formation in Vero cells during starvation. Our findings provide a mechanistic understanding for the potent autophagy inhibitory activity of A179L and serve as a platform for more detailed investigations into the role of autophagy during ASFV infection.

Crystal Structure of African Swine Fever Virus A179L with the Autophagy Regulator Beclin.,Banjara S, Shimmon GL, Dixon LK, Netherton CL, Hinds MG, Kvansakul M Viruses. 2019 Aug 27;11(9). pii: v11090789. doi: 10.3390/v11090789. PMID:31461953^[4]

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

References

↑ Galindo I, Hernaez B, Diaz-Gil G, Escribano JM, Alonso C. A179L, a viral Bcl-2 homologue, targets the core Bcl-2 apoptotic machinery and its upstream BH3 activators with selective binding restrictions for Bid and Noxa. Virology. 2008 Jun 5;375(2):561-72. doi: 10.1016/j.virol.2008.01.050. Epub 2008, Mar 10. PMID:18329683 doi:http://dx.doi.org/10.1016/j.virol.2008.01.050
↑ Banjara S, Caria S, Dixon LK, Hinds MG, Kvansakul M. Structural insight into African Swine Fever virus A179L mediated inhibition of apoptosis. J Virol. 2017 Jan 4. pii: JVI.02228-16. doi: 10.1128/JVI.02228-16. PMID:28053104 doi:http://dx.doi.org/10.1128/JVI.02228-16
↑ Revilla Y, Cebrian A, Baixeras E, Martinez C, Vinuela E, Salas ML. Inhibition of apoptosis by the African swine fever virus Bcl-2 homologue: role of the BH1 domain. Virology. 1997 Feb 17;228(2):400-4. doi: 10.1006/viro.1996.8395. PMID:9123849 doi:http://dx.doi.org/10.1006/viro.1996.8395
↑ Banjara S, Shimmon GL, Dixon LK, Netherton CL, Hinds MG, Kvansakul M. Crystal Structure of African Swine Fever Virus A179L with the Autophagy Regulator Beclin. Viruses. 2019 Aug 27;11(9). pii: v11090789. doi: 10.3390/v11090789. PMID:31461953 doi:http://dx.doi.org/10.3390/v11090789

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6tzc"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6tzc is ON HOLD
+==Crystal Structure of African Swine Fever Virus A179L with the Autophagy Regulator Beclin==
+<StructureSection load='6tzc' size='340' side='right'caption='[[6tzc]], [[Resolution|resolution]] 2.41&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6tzc]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TZC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6TZC FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MAL:MALTOSE'>MAL</scene></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=6tzc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tzc OCA], [http://pdbe.org/6tzc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6tzc RCSB], [http://www.ebi.ac.uk/pdbsum/6tzc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6tzc ProSAT]</span></td></tr>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/MALE_ECOLI MALE_ECOLI]] Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides. [[http://www.uniprot.org/uniprot/BECN1_PIG BECN1_PIG]] Plays a central role in autophagy. Acts as core subunit of the PI3K complex that mediates formation of phosphatidylinositol 3-phosphate; different complex forms are believed to play a role in multiple membrane trafficking pathways: PI3KC3-C1 is involved in initiation of autophagosomes and PI3KC3-C2 in maturation of autophagosomes and endocytosis. Involved in regulation of degradative endocytic trafficking and required for the abcission step in cytokinesis, probably in the context of PI3KC3-C2. Essential for the formation of PI3KC3-C2 but not PI3KC3-C1 PI3K complex forms. Involved in endocytosis. May play a role in antiviral host defense (By similarity).[UniProtKB:O88597][UniProtKB:Q14457][UniProtKB:Q91XJ1]  Beclin-1-C 35 kDa localized to mitochondria can promote apoptosis; it induces the mitochondrial translocation of BAX and the release of proapoptotic factors.[UniProtKB:O88597][UniProtKB:Q14457] [[http://www.uniprot.org/uniprot/ARBH_ASFB7 ARBH_ASFB7]] Suppresses apoptosis in host cell and thus facilitates production of progeny virions (PubMed:9123849, PubMed:18329683). Has the ability to potentially bind to all the members of the proapoptotic Bcl-2 family (PubMed:28053104, PubMed:18329683).<ref>PMID:18329683</ref> <ref>PMID:28053104</ref> <ref>PMID:9123849</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Subversion of programmed cell death-based host defence systems is a prominent feature of infections by large DNA viruses. African swine fever virus (ASFV) is a large DNA virus and sole member of the Asfarviridae family that harbours the B-cell lymphoma 2 or Bcl-2 homolog A179L. A179L has been shown to bind to a range of cell death-inducing host proteins, including pro-apoptotic Bcl-2 proteins as well as the autophagy regulator Beclin. Here we report the crystal structure of A179L bound to the Beclin BH3 motif. A179L engages Beclin using the same canonical ligand-binding groove that is utilized to bind to pro-apoptotic Bcl-2 proteins. The mode of binding of Beclin to A179L mirrors that of Beclin binding to human Bcl-2 and Bcl-xL as well as murine gamma-herpesvirus 68. The introduction of bulky hydrophobic residues into the A179L ligand-binding groove via site-directed mutagenesis ablates binding of Beclin to A179L, leading to a loss of the ability of A179L to modulate autophagosome formation in Vero cells during starvation. Our findings provide a mechanistic understanding for the potent autophagy inhibitory activity of A179L and serve as a platform for more detailed investigations into the role of autophagy during ASFV infection.
-Authors:
+Crystal Structure of African Swine Fever Virus A179L with the Autophagy Regulator Beclin.,Banjara S, Shimmon GL, Dixon LK, Netherton CL, Hinds MG, Kvansakul M Viruses. 2019 Aug 27;11(9). pii: v11090789. doi: 10.3390/v11090789. PMID:31461953<ref>PMID:31461953</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 6tzc" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Banjara, S]]
+[[Category: Hinds, M G]]
+[[Category: Kvansakul, M]]
+[[Category: Apoptosis]]
+[[Category: Autophagy]]
+[[Category: Bcl-2 virus]]
+[[Category: Structural protein]]
+[[Category: Structural protein-apoptosis complex]]

6tzc

From Proteopedia

Revision as of 15:39, 20 November 2019

Crystal Structure of African Swine Fever Virus A179L with the Autophagy Regulator Beclin

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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