Dataset Information

Molecular basis of dimerization of initiator caspase was revealed by crystal structure of caspase-8 pro-domain.

ABSTRACT: The assembly of death-inducing signaling complex (DISC) for activation of initiator caspase is a key step for the receptor-mediated apoptosis signaling. Many death effector domain (DED)-containing proteins are involved in DISC assembly and controlling. One of the main DISC component, caspase-8, contains DED and DED-mediated dimerization and oligomerization in the DISC is critical for the activation of this initiator caspase. There have been intensive studies to understand DED-mediated dimerization and oligomerization for the DISC assembly but no clear answer has been provided and there are many controversial arguments. Here, we suggested novel dimerization process of tandem DED of caspase-8 with crystallographic study.

SUBMITTER: Park HH

PROVIDER: S-EPMC6748139 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Molecular basis of dimerization of initiator caspase was revealed by crystal structure of caspase-8 pro-domain.

Park Hyun Ho HH

Cell death and differentiation 20180911 7

The assembly of death-inducing signaling complex (DISC) for activation of initiator caspase is a key step for the receptor-mediated apoptosis signaling. Many death effector domain (DED)-containing proteins are involved in DISC assembly and controlling. One of the main DISC component, caspase-8, contains DED and DED-mediated dimerization and oligomerization in the DISC is critical for the activation of this initiator caspase. There have been intensive studies to understand DED-mediated dimerizati ...[more]

PMID: 30206319

Similar Datasets

Project description:BACKGROUND:IPS-1/MAVS/VISA/Cardif is an adaptor protein that plays a crucial role in the induction of interferons in response to viral infection. In the initial stage of the intracellular antiviral response two RNA helicases, retinoic acid inducible gene-I (RIG-I) and melanoma differentiation-association gene 5 (MDA5), are independently able to bind viral RNA in the cytoplasm. The 62 kDa protein IPS-1/MAVS/VISA/Cardif contains an N-terminal caspase activation and recruitment (CARD) domain that associates with the CARD regions of RIG-I and MDA5, ultimately leading to the induction of type I interferons. As a first step towards understanding the molecular basis of this important adaptor protein we have undertaken structural studies of the IPS-1 MAVS/VISA/Cardif CARD region. RESULTS:The crystal structure of human IPS-1/MAVS/VISA/Cardif CARD has been determined to 2.1A resolution. The protein was expressed and crystallized as a maltose-binding protein (MBP) fusion protein. The MBP and IPS-1 components each form a distinct domain within the structure. IPS-1/MAVS/VISA/Cardif CARD adopts a characteristic six-helix bundle with a Greek-key topology and, in common with a number of other known CARD structures, contains two major polar surfaces on opposite sides of the molecule. One face has a surface-exposed, disordered tryptophan residue that may explain the poor solubility of untagged expression constructs. CONCLUSION:The IPS-1/MAVS/VISA/Cardif CARD domain adopts the classic CARD fold with an asymmetric surface charge distribution that is typical of CARD domains involved in homotypic protein-protein interactions. The location of the two polar areas on IPS-1/MAVS/VISA/Cardif CARD suggest possible types of associations that this domain makes with the two CARD domains of MDA5 or RIG-I. The N-terminal CARD domains of RIG-I and MDA5 share greatest sequence similarity with IPS-1/MAVS/VISA/Cardif CARD and this has allowed modelling of their structures. These models show a very different charge profile for the equivalent surfaces compared to IPS-1/MAVS/VISA/Cardif CARD.

Dataset Information

Molecular basis of dimerization of initiator caspase was revealed by crystal structure of caspase-8 pro-domain.

Publications

Molecular basis of dimerization of initiator caspase was revealed by crystal structure of caspase-8 pro-domain.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure