6TZC

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

Summary for 6TZC

• Entry DOI: 10.2210/pdb6tzc/pdb
• Related PRD ID: PRD_900001
• Descriptor: Maltose/maltodextrin-binding periplasmic protein, Apoptosis regulator Bcl-2 homolog, Beclin-1, ... (5 entities in total)
• Functional Keywords: apoptosis, autophagy, bcl-2 virus, structural protein, structural protein-apoptosis complex, structural protein/apoptosis
• Biological source: Escherichia coli (strain K12); More
• Total number of polymer chains: 3
• Total formula weight: 61999.06

Authors

Banjara, S.,Kvansakul, M.,Hinds, M.G. (deposition date: 2019-08-12, release date: 2019-11-20, Last modification date: 2023-10-11)

Primary citation

Banjara, S.,Shimmon, G.L.,Dixon, L.K.,Netherton, C.L.,Hinds, M.G.,Kvansakul, M.
Crystal Structure of African Swine Fever Virus A179L with the Autophagy Regulator Beclin.
Viruses, 11:-, 2019

PubMed Abstract: 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 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-x as well as murine γ-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.

PubMed: 31461953
DOI: 10.3390/v11090789

Experimental method

X-RAY DIFFRACTION (2.41 Å)