Dataset Information

Electrostatic and functional analysis of the seven-bladed WD beta-propellers.

ABSTRACT: beta-propeller domains composed of WD repeats are highly ubiquitous and typically used as multi-site docking platforms to coordinate and integrate the activities of groups of proteins. Here, we have used extensive homology modelling of the WD40-repeat family of seven-bladed beta-propellers coupled with subsequent structural classification and clustering of these models to define subfamilies of beta-propellers with common structural, and probable, functional characteristics. We show that it is possible to assign seven-bladed WD beta-propeller proteins into functionally different groups based on the information gained from homology modelling. We examine general structural diversity within the WD40-repeat family of seven-bladed beta-propellers and demonstrate that seven-bladed beta-propellers composed of WD-repeats are structurally distinct from other seven-bladed beta-propellers. We further provide some insights into the multifunctional diversity of the seven-bladed WD beta-propeller surfaces. This report once again reinforces the importance of structural data and the usefulness of homology models in functional classification.

SUBMITTER: Valeyev NV

PROVIDER: S-EPMC2614187 | biostudies-literature | 2008 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Electrostatic and functional analysis of the seven-bladed WD beta-propellers.

Valeyev Najl V NV Downing A Kristina AK Sondek John J Deane Charlotte C

Evolutionary bioinformatics online 20080613

beta-propeller domains composed of WD repeats are highly ubiquitous and typically used as multi-site docking platforms to coordinate and integrate the activities of groups of proteins. Here, we have used extensive homology modelling of the WD40-repeat family of seven-bladed beta-propellers coupled with subsequent structural classification and clustering of these models to define subfamilies of beta-propellers with common structural, and probable, functional characteristics. We show that it is po ...[more]

PMID: 19204818

Similar Datasets

Project description:The human EED protein, a member of the superfamily of Polycomb group proteins, is involved in multiple cellular protein complexes. Its C-terminal domain, which is common to the four EED isoforms, contains seven repeats of a canonical WD-40 motif. EED is an interactor of three HIV-1 proteins, matrix (MA), integrase (IN) and Nef. An antiviral activity has been found to be associated with isoforms EED3 and EED4 at the late stage of HIV-1 replication, due to a negative effect on virus assembly and genomic RNA packaging. The aim of the present study was to determine the regions of the EED C-terminal core domain which were accessible and available to protein interactions, using three-dimensional (3D) protein homology modelling with a WD-40 protein of known structure, and epitope mapping of anti-EED antibodies.Our data suggested that the C-terminal domain of EED was folded as a seven-bladed beta-propeller protein. During the completion of our work, crystallographic data of EED became available from co-crystals of the EED C-terminal core with the N-terminal domain of its cellular partner EZH2. Our 3D-model was in good congruence with the refined structural model determined from crystallographic data, except for a unique alpha-helix in the fourth beta-blade. More importantly, the position of flexible loops and accessible beta-strands on the beta-propeller was consistent with our mapping of immunogenic epitopes and sites of interaction with HIV-1 MA and IN. Certain immunoreactive regions were found to overlap with the EZH2, MA and IN binding sites, confirming their accessibility and reactivity at the surface of EED. Crystal structure of EED showed that the two discrete regions of interaction with MA and IN did not overlap with each other, nor with the EZH2 binding pocket, but were contiguous, and formed a continuous binding groove running along the lateral face of the beta-propeller.Identification of antibody-, MA-, IN- and EZH2-binding sites at the surface of the EED isoform 3 provided a global picture of the immunogenic and protein-protein interacting regions in the EED C-terminal domain, organized as a seven-bladed beta-propeller protein. Mapping of the HIV-1 MA and IN binding sites on the 3D-model of EED core predicted that EED-bound MA and IN ligands would be in close vicinity at the surface of the beta-propeller, and that the occurrence of a ternary complex MA-EED-IN would be possible.

Dataset Information

Electrostatic and functional analysis of the seven-bladed WD beta-propellers.

Publications

Electrostatic and functional analysis of the seven-bladed WD beta-propellers.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets