Binding to retinoblastoma pocket domain does not alter the inter-domain flexibility of the J domain of SV40 large T antigen.

Williams CK, Vaithiyalingam S, Hammel M, Pipas J, Chazin WJ
Arch Biochem Biophys. 2012 518 (2): 111-8

PMID: 22227098 · PMCID: PMC3279518 · DOI:10.1016/j.abb.2011.12.014

Simian Virus 40 uses the large T antigen (Tag) to bind and inactivate retinoblastoma tumor suppressor proteins (Rb), which can result in cellular transformation. Tag is a modular protein with four domains connected by flexible linkers. The N-terminal J domain of Tag is necessary for Rb inactivation. Binding of Rb is mediated by an LXCXE consensus motif immediately C-terminal to the J domain. Nuclear magnetic resonance (NMR) and small angle X-ray scattering (SAXS) were used to study the structural dynamics and interaction of Rb with the LXCXE motif, the J domain and a construct (N(260)) extending from the J domain through the origin binding domain (OBD). NMR and SAXS data revealed substantial flexibility between the domains in N(260). Binding of pRb to a construct containing the LXCXE motif and the J domain revealed weak interactions between pRb and the J domain. Analysis of the complex of pRb and N(260) indicated that the OBD is not involved and retains its dynamic independence from the remainder of Tag. These results support a 'chaperone' model in which the J domain of Tag changes its orientation as it acts upon different protein complexes.

Copyright © 2011 Elsevier Inc. All rights reserved.

MeSH Terms (8)

Amino Acid Motifs Antigens, Polyomavirus Transforming Multiprotein Complexes Nuclear Magnetic Resonance, Biomolecular Protein Binding Protein Structure, Quaternary Protein Structure, Tertiary Retinoblastoma Protein

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