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PDBsum entry 3bl2
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protein Protein-protein interface(s) links
Viral protein/apoptosis PDB id
3bl2

 

 

 

 

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Contents
Protein chains
131 a.a.
19 a.a.
Waters ×59
PDB id:
3bl2
Name: Viral protein/apoptosis
Title: Crystal structure of m11, the bcl-2 homolog of murine gamma- herpesvirus 68, complexed with mouse beclin1 (residues 106-124)
Structure: V-bcl-2. Chain: a, b. Fragment: unp residues 5-135. Synonym: bcl-2 homolog, gene 16?, m11. Engineered: yes. Beclin-1. Chain: c, d. Fragment: bcl-2 binding region, bh3-like domain, unp residues 106- 124.
Source: Murid herpesvirus 4. Murine herpesvirus 68. Organism_taxid: 33708. Gene: v-bcl-2, gammahv.M11, m11. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Mus musculus. House mouse. Organism_taxid: 10090.
Resolution:
2.30Å     R-factor:   0.204     R-free:   0.247
Authors: B.-H.Oh,J.-S.Woo,B.Ku
Key ref: B.Ku et al. (2008). Structural and biochemical bases for the inhibition of autophagy and apoptosis by viral BCL-2 of murine gamma-herpesvirus 68. Plos Pathog, 4, e25. PubMed id: 18248095
Date:
10-Dec-07     Release date:   12-Feb-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
P89884  (ARBH_MHV68) -  Apoptosis regulator Bcl-2 homolog from Murid herpesvirus 4
Seq:
Struc: 		171 a.a.
131 a.a.
Protein chains
Pfam   ArchSchema ?
O88597  (BECN1_MOUSE) -  Beclin-1 from Mus musculus
Seq:
Struc: 		448 a.a.
19 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 

 
Plos Pathog 4:e25 (2008)
PubMed id: 18248095  
 
 
Structural and biochemical bases for the inhibition of autophagy and apoptosis by viral BCL-2 of murine gamma-herpesvirus 68.
B.Ku, J.S.Woo, C.Liang, K.H.Lee, H.S.Hong, X.E, K.S.Kim, J.U.Jung, B.H.Oh.
 
  ABSTRACT  
 
All gammaherpesviruses express homologues of antiapoptotic B-cell lymphoma-2 (BCL-2) to counter the clearance of infected cells by host antiviral defense machineries. To gain insights into the action mechanisms of these viral BCL-2 proteins, we carried out structural and biochemical analyses on the interactions of M11, a viral BCL-2 of murine gamma-herpesvirus 68, with a fragment of proautophagic Beclin1 and BCL-2 homology 3 (BH3) domain-containing peptides derived from an array of proapoptotic BCL-2 family proteins. Mainly through hydrophobic interactions, M11 bound the BH3-like domain of Beclin1 with a dissociation constant of 40 nanomole, a markedly tighter affinity compared to the 1.7 micromolar binding affinity between cellular BCL-2 and Beclin1. Consistently, M11 inhibited autophagy more efficiently than BCL-2 in NIH3T3 cells. M11 also interacted tightly with a BH3 domain peptide of BAK and those of the upstream BH3-only proteins BIM, BID, BMF, PUMA, and Noxa, but weakly with that of BAX. These results collectively suggest that M11 potently inhibits Beclin1 in addition to broadly neutralizing the proapoptotic BCL-2 family in a similar but distinctive way from cellular BCL-2, and that the Beclin1-mediated autophagy may be a main target of the virus.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21439939 B.Juhásová, I.Bhatia-Kiššová, K.Polčicová, M.Mentel, M.Forte, and P.Polčic (2011).
Reconstitution of interactions of Murine gammaherpesvirus 68 M11 with Bcl-2 family proteins in yeast.
  Biochem Biophys Res Commun, 407, 783-787.  
21060336 B.Ku, C.Liang, J.U.Jung, and B.H.Oh (2011).
Evidence that inhibition of BAX activation by BCL-2 involves its tight and preferential interaction with the BH3 domain of BAX.
  Cell Res, 21, 627-641.
PDB code: 2xa0
21219186 E.Barton, P.Mandal, and S.H.Speck (2011).
Pathogenesis and host control of gammaherpesviruses: lessons from the mouse.
  Annu Rev Immunol, 29, 351-397.  
21311563 R.Kang, H.J.Zeh, M.T.Lotze, and D.Tang (2011).
The Beclin 1 network regulates autophagy and apoptosis.
  Cell Death Differ, 18, 571-580.  
20502964 B.Krampe, and M.Al-Rubeai (2010).
Cell death in mammalian cell culture: molecular mechanisms and cell line engineering strategies.
  Cytotechnology, 62, 175-188.  
20403451 C.Dinkins, J.Arko-Mensah, and V.Deretic (2010).
Autophagy and HIV.
  Semin Cell Dev Biol, 21, 712-718.  
20097051 C.He, and B.Levine (2010).
The Beclin 1 interactome.
  Curr Opin Cell Biol, 22, 140-149.  
20865416 H.J.Kim, S.Lee, and J.U.Jung (2010).
When autophagy meets viruses: a double-edged sword with functions in defense and offense.
  Semin Immunopathol, 32, 323-341.  
20860481 H.R.Lee, S.Lee, P.M.Chaudhary, P.Gill, and J.U.Jung (2010).
Immune evasion by Kaposi's sarcoma-associated herpesvirus.
  Future Microbiol, 5, 1349-1365.  
20857294 M.Gannage, and C.Münz (2010).
MHC presentation via autophagy and how viruses escape from it.
  Semin Immunopathol, 32, 373-381.  
20015983 Q.Jia, M.L.Freeman, E.J.Yager, I.McHardy, L.Tong, D.Martinez-Guzman, T.Rickabaugh, S.Hwang, M.A.Blackman, R.Sun, and T.T.Wu (2010).
Induction of protective immunity against murine gammaherpesvirus 68 infection in the absence of viral latency.
  J Virol, 84, 2453-2465.  
20356743 S.F.Funderburk, Q.J.Wang, and Z.Yue (2010).
The Beclin 1-VPS34 complex--at the crossroads of autophagy and beyond.
  Trends Cell Biol, 20, 355-362.  
20717741 T.T.Wu, M.A.Blackman, and R.Sun (2010).
Prospects of a novel vaccination strategy for human gamma-herpesviruses.
  Immunol Res, 48, 122-146.  
18772897 A.Orvedahl, and B.Levine (2009).
Eating the enemy within: autophagy in infectious diseases.
  Cell Death Differ, 16, 57-69.  
19105657 C.Münz (2009).
Enhancing immunity through autophagy.
  Annu Rev Immunol, 27, 423-449.  
19347031 I.A.Ciechomska, G.C.Goemans, J.N.Skepper, and A.M.Tolkovsky (2009).
Bcl-2 complexed with Beclin-1 maintains full anti-apoptotic function.
  Oncogene, 28, 2128-2141.  
19838173 J.S.Lee, Q.Li, J.Y.Lee, S.H.Lee, J.H.Jeong, H.R.Lee, H.Chang, F.C.Zhou, S.J.Gao, C.Liang, and J.U.Jung (2009).
FLIP-mediated autophagy regulation in cell death control.
  Nat Cell Biol, 11, 1355-1362.  
  19837376 M.Gannagé, D.Dormann, R.Albrecht, J.Dengjel, T.Torossi, P.C.Rämer, M.Lee, T.Strowig, F.Arrey, G.Conenello, M.Pypaert, J.Andersen, A.García-Sastre, and C.Münz (2009).
Matrix protein 2 of influenza A virus blocks autophagosome fusion with lysosomes.
  Cell Host Microbe, 6, 367-380.  
19297471 M.N.Takahashi, W.Jackson, D.T.Laird, T.D.Culp, C.Grose, J.I.Haynes, and L.Benetti (2009).
Varicella-zoster virus infection induces autophagy in both cultured cells and human skin vesicles.
  J Virol, 83, 5466-5476.  
19806153 N.C.Elde, and H.S.Malik (2009).
The evolutionary conundrum of pathogen mimicry.
  Nat Rev Microbiol, 7, 787-797.  
19750559 S.B.Kudchodkar, and B.Levine (2009).
Viruses and autophagy.
  Rev Med Virol, 19, 359-378.  
  19527881 V.Deretic, and B.Levine (2009).
Autophagy, immunity, and microbial adaptations.
  Cell Host Microbe, 5, 527-549.  
19816569 X.E, S.Hwang, S.Oh, J.S.Lee, J.H.Jeong, Y.Gwack, T.F.Kowalik, R.Sun, J.U.Jung, and C.Liang (2009).
Viral Bcl-2-mediated evasion of autophagy aids chronic infection of gammaherpesvirus 68.
  PLoS Pathog, 5, e1000609.  
19266576 Y.G.Kim, J.Y.Kim, C.Mohan, and G.M.Lee (2009).
Effect of Bcl-xL overexpression on apoptosis and autophagy in recombinant Chinese hamster ovary cells under nutrient-deprived condition.
  Biotechnol Bioeng, 103, 757-766.  
18503639 A.Orvedahl, and B.Levine (2008).
Autophagy and viral neurovirulence.
  Cell Microbiol, 10, 1747-1756.  
18948197 C.Liang, J.S.Lee, and J.U.Jung (2008).
Immune evasion in Kaposi's sarcoma-associated herpes virus associated oncogenesis.
  Semin Cancer Biol, 18, 423-436.  
19641503 E.Lomonosova, and G.Chinnadurai (2008).
BH3-only proteins in apoptosis and beyond: an overview.
  Oncogene, 27, S2-19.  
18931086 N.Jacobs, N.W.Bartlett, R.H.Clark, and G.L.Smith (2008).
Vaccinia virus lacking the Bcl-2-like protein N1 induces a stronger natural killer cell response to infection.
  J Gen Virol, 89, 2877-2881.  
18704168 S.C.Graham, M.W.Bahar, S.Cooray, R.A.Chen, D.M.Whalen, N.G.Abrescia, D.Alderton, R.J.Owens, D.I.Stuart, G.L.Smith, and J.M.Grimes (2008).
Vaccinia virus proteins A52 and B14 Share a Bcl-2-like fold but have evolved to inhibit NF-kappaB rather than apoptosis.
  PLoS Pathog, 4, e1000128.
PDB codes: 2vvw 2vvx 2vvy
19641499 S.Sinha, and B.Levine (2008).
The autophagy effector Beclin 1: a novel BH3-only protein.
  Oncogene, 27, S137-S148.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.

 

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