The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Molecular basis of the regulation of Beclin 1-dependent autophagy by the γ-herpesvirus 68 Bcl-2 homolog M11
Open accessAbstract
Gamma-herpesviruses (gammaHVs), including important human pathogens such as Epstein Barr virus, Kaposi's sarcoma-associated HV, and the murine gammaHV68, encode homologs of the antiapoptotic, cellular Bcl-2 (cBcl-2) to promote viral replication and pathogenesis. The precise molecular details by which these proteins function in viral infection are poorly understood. Autophagy, a lysosomal degradation pathway, is inhibited by the interaction of cBcl-2s with a key autophagy effector, Beclin 1, and can also be inhibited by gammaHV Bcl-2s. Here we investigate the gammaHV68 M11-Beclin 1 interaction in atomic detail, using biochemical and structural approaches. We show that the Beclin 1 BH3 domain is the primary determinant of binding to M11 and other Bcl-2s, and this domain binds in a hydrophobic groove on M11, reminiscent of the binding of different BH3 domains to other Bcl-2s. Unexpectedly, regions outside of, but contiguous with, the Beclin 1 BH3 domain also contribute to this interaction. We find that M11 binds to Beclin 1 more strongly than do KSHV Bcl-2 or cBcl-2. Further, the differential affinity of M11 for different BH3 domains is caused by subtle, yet significant, variations in the atomic details of each interaction. Consistent with our structural analysis, we find that Beclin 1 residues L116 and F123, and M11 residue pairs G86 + R87 and Y60 + L74, are required for M11 to bind to Beclin 1 and downregulate autophagy. Thus, our results suggest that M11 inhibits autophagy through a mechanism that involves the binding of the Beclin 1 BH3 domain in the M11 hydrophobic surface groove.
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Cites
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Self-citationAutophagy fights disease through cellular self-digestion
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Self-citationInduction of autophagy and inhibition of tumorigenesis by beclin 1
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Self-citationYue, Z., Jin, S., Yang, C., Levine, A. J., & Heintz, N. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2436255100 · Cited by 2,116
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Beclin–phosphatidylinositol 3‐kinase complex functions at the trans‐Golgi network
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UVRAG: A new player in autophagy and tumor cell growth
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Cited by
The Beclin 1 network regulates autophagy and apoptosis
Kang, R., Zeh, H. J., Lotze, M. T., & Tang, D. (2011) · Cell Death & Differentiation · doi:10.1038/cdd.2010.191 · Cited by 2,485
The Beclin 1–VPS34 complex – at the crossroads of autophagy and beyond
Funderburk, S. F., Wang, Q. J., & Yue, Z. (2010) · Trends in Cell Biology · doi:10.1016/j.tcb.2010.03.002 · Cited by 782
Disruption of the beclin 1–BCL2 autophagy regulatory complex promotes longevity in mice
Fernández, Á. F., Sebti, S., Wei, Y., Zou, Z., Shi, M., McMillan, K. L., He, C., Ting, T., Liu, Y., Chiang, W.-C., et al. (2018) · Nature · doi:10.1038/s41586-018-0162-7 · Cited by 630
Self-citationMultiple Functions of BCL-2 Family Proteins
Hardwick, J. M., & Soane, L. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a008722 · Cited by 564
Matrix Protein 2 of Influenza A Virus Blocks Autophagosome Fusion with Lysosomes
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Metadata
- Authors
- Sinha, S. C., Colbert, C. L., Becker, N., Wei, Y., & Levine, B.
- Venue
- Autophagy
- Publisher
- Informa UK Limited
- Published
- 2008-11-16
- Volume
- 4
- Issue
- 8
- Pages
- 989-997
- ISSN
- 1554-8627 (ISSN-L)
- 1554-8635
- OpenAlex
- W2126897634
- Cited by
- 162
- References
- 9
- FWCI
- 8.76
- Type
- journal article
- Language
- en
- Open access
- hybrid
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