2017
DOI: 10.1074/jbc.m116.768879
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Structural basis of apoptosis inhibition by the fowlpox virus protein FPV039

Abstract: Edited by Norma AllewellProgrammed cell death or apoptosis of infected host cells is an important defense mechanism in response to viral infections. This process is regulated by proapoptotic and prosurvival members of the B-cell lymphoma 2 (Bcl-2) protein family. To counter premature death of a virus-infected cell, poxviruses use a range of different molecular strategies including the mimicry of prosurvival Bcl-2 proteins. One such viral prosurvival protein is the fowlpox virus protein FPV039, which is a poten… Show more

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Cited by 33 publications
(55 citation statements)
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“…BH3 peptide complexes exemplified by Bcl-x L R139-Bax D68 ( Figure 4A). This Arg:Asp interaction is also observed in the complexes with BH3 peptides of the virus-encoded Bcl-2 homologs A179L [10,40], BHRF1 [12] and FPV039 [22]. Unlike the canonical ionic interaction [41,42], the geometric configuration of the ionic bond in SPPV14 is different, allowing SPPV14 to engage BH3 motif in manner that resembles the use of the BH1 motif in mammalian prosurvival Bcl-2 interactions despite the lack of a recognizable BH1 sequence motif ( Figure 4A,B).…”
Section: Resultsmentioning
confidence: 64%
See 1 more Smart Citation
“…BH3 peptide complexes exemplified by Bcl-x L R139-Bax D68 ( Figure 4A). This Arg:Asp interaction is also observed in the complexes with BH3 peptides of the virus-encoded Bcl-2 homologs A179L [10,40], BHRF1 [12] and FPV039 [22]. Unlike the canonical ionic interaction [41,42], the geometric configuration of the ionic bond in SPPV14 is different, allowing SPPV14 to engage BH3 motif in manner that resembles the use of the BH1 motif in mammalian prosurvival Bcl-2 interactions despite the lack of a recognizable BH1 sequence motif ( Figure 4A,B).…”
Section: Resultsmentioning
confidence: 64%
“…Large DNA viruses encode a number of sequence and structural homologs of Bcl -2, including examples among the adenoviridae [8], asfarviridae [9,10], herpesviridae [11,12] and iridoviridae [13,14]. Among the poxviridae, the majority of genera have been shown to harbor one or more examples, including the orthopoxviridae [15,16], leporipoxviridae [17,18], cervidpoxviridae [19,20], avipoxviridae [21,22], parapoxviridae [23] and chordopoxviridae [24], with the vaccinia virus F1L and myxomavirus M11L the prototypical members of the family. Amongst the capripoxviridae, sheeppoxvirus has been shown to encode the potent apoptosis inhibitory protein SPPV14, a Bcl-2 homolog [25].…”
Section: Introductionmentioning
confidence: 99%
“…Despite lacking detectable sequence identity to cellular Bcl-2 or Bcl-x L , M11L adopts a Bcl-2 fold [57,129] (Figure 2a,b and Figure 3g,h) and sequesters Bax and Bak to prevent apoptosis [57], unlike VACV F1L which operates via Bim neutralization [121]. Other poxvirus-encoded vBcl-2 members include fowlpox FPV039 [58,59] and canarypox virus (CNPV058) [61], sheep poxvirus [62], and orf virus ORFV125 [63]. Outside the herpes and poxviridae, ASFV encodes A179L [130], a Bcl-2 homolog that uses the canonical ligand-binding groove to engage all major host proapoptotic Bcl-2 members [51] as well as Beclin-1 [131], thus acting as a dual apoptosis/autophagy inhibitor [50,132].…”
Section: Poxvirus Bcl-2 Homologsmentioning
confidence: 99%
“…Poxviruses encode antiapoptotic proteins that often lack any overt sequence identity with Bcl-2. These include F1L from variola virus and vaccinia virus [13][14][15][16][17], N1L from vaccinia virus [18][19][20], M11L from myxoma virus [21][22][23], as well as fowlpoxvirus FPV039 [24,25], canarypoxvirus CNP058 [26], orf virus ORF125 [27,28], deerpoxvirus DPV022 [29,30], and sheeppoxvirus SPPV14 [31]. Amongst the iridoviridae, grouper iridovirus encodes pro-survival GIV66 [32,33].…”
Section: Introductionmentioning
confidence: 99%