Structural insights into viral subversion of death receptor signalling

Lambert, L. K. and Hill, J. M. (2008). Structural insights into viral subversion of death receptor signalling. In: Combined Conference Abstracts. Proceedings of the Australian Society for Biochemistry and Molecular Biology. ComBio2008, Canberra, Australia, (). 21-25 September, 2008.


Author Lambert, L. K.
Hill, J. M.
Title of paper Structural insights into viral subversion of death receptor signalling
Conference name ComBio2008
Conference location Canberra, Australia
Conference dates 21-25 September, 2008
Proceedings title Combined Conference Abstracts. Proceedings of the Australian Society for Biochemistry and Molecular Biology
Place of Publication Kent Town, S.A., Australia
Publisher Australian Society for Biochemistry and Molecular Biology
Publication Year 2008
Sub-type Other
ISSN 1328-4924
Volume 40
Language eng
Abstract/Summary Death receptor signalling is initiated by the assembly of the death-inducing signalling complex (DISC), culminating in the activation of the initiator caspases, caspase-8 or caspase-10. A number of viruses express distinct families of inhibitory proteins to suppress apoptosis and promote their replication and survival in host cells. One important family of such proteins is the viral FLICE-inhibitory proteins (v-FLIPs) present in several γ-herpesviruses and poxviruses. v-FLIPs, such as MC159 from molluscum contagiosum virus, block the activation of death receptors at the level of DISC assembly. The hallmark of v-FLIPs is two death effector domains (DEDs), which are also present in the prodomains of caspase-8 and caspase-10. The DEDs of MC159 have been shown to interact with the DED of the adaptor protein FADD and the prodomain of caspase-8 to hinder caspase recruitment and activation. However, the underlying mechanisms remain unclear. At present there is only limited structural information on DISC proteins and complexes have remained elusive. Here we will present the structure of the MC159/FADD complex characterised using NMR spectroscopy. A combination of chemical shift perturbation, transferred cross-saturation and residual dipolar couplings have been used to define the interacting surfaces and determine the structure of the 44 kDa complex. Our results offer new insights into the mechanism by which v-FLIPs subvert death receptor signalling.
Subjects 11 Medical and Health Sciences
Q-Index Code EX
Q-Index Status Provisional Code
Institutional Status Unknown

 
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Created: Thu, 04 Mar 2010, 12:21:40 EST by Jon Swabey on behalf of Faculty of Science