Viral Bcl2s’ transmembrane domain interact with host Bcl2 proteins to control cellular apoptosis

• Published in: Nature communications 2020-11, Vol.11 (1), p.6056-15, Article 6056
• Main Authors: García-Murria, Maria Jesús, Duart, Gerard, Grau, Brayan, Diaz-Beneitez, Elisabet, Rodríguez, Dolores, Mingarro, Ismael, Martínez-Gil, Luis
• Format: Article
• Language: English
• Subjects: 13; 14; 14/19; 631/326/596/2557; 631/45/612/1256; Amino Acid Sequence; Analogs; Apoptosis; B-cell lymphoma; Cell death; Cell Line; Cell Membrane - drug effects; Cell Membrane - metabolism; Deregulation; Doxorubicin - pharmacology; Fluorescence; Humanities and Social Sciences; Humans; Hydrophobic and Hydrophilic Interactions; Hydrophobicity; Lymphocytes B; Lymphoma; Membranes; Mortality; multidisciplinary; Oligomerization; Protein Binding - drug effects; Protein Domains; Protein Multimerization - drug effects; Proteins; Proto-Oncogene Proteins c-bcl-2 - chemistry; Proto-Oncogene Proteins c-bcl-2 - metabolism; Science; Science (multidisciplinary); Transmembrane domains; Viral Proteins - chemistry; Viral Proteins - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-19881-9

Viral control of programmed cell death relies in part on the expression of viral analogs of the B-cell lymphoma 2 (Bcl2) protein known as viral Bcl2s (vBcl2s). vBcl2s control apoptosis by interacting with host pro- and anti-apoptotic members of the Bcl2 family. Here, we show that the carboxyl-terminal hydrophobic region of herpesviral and poxviral vBcl2s can operate as transmembrane domains (TMDs) and participate in their homo-oligomerization. Additionally, we show that the viral TMDs mediate interactions with cellular pro- and anti-apoptotic Bcl2 TMDs within the membrane. Furthermore, these intra-membrane interactions among viral and cellular proteins are necessary to control cell death upon an apoptotic stimulus. Therefore, their inhibition represents a new potential therapy against viral infections, which are characterized by short- and long-term deregulation of programmed cell death. Viral analogs of B-cell lymphoma 2 (Bcl2), known as vBcl2s, control apoptosis by interacting with host pro- and anti-apoptotic members of the Bcl2 family. Here, García-Murria et al. report on transmembrane domains (TMDs) in the C-terminal hydrophobic region of herpes- and poxviral vBcl2s, which mediate homo-oligomerization and interactions with cellular Bcl2 TMDs to control apoptosis.