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Type: Journal article
Title: A flexible brace maintains the assembly of a hexameric replicative helicase during DNA unwinding
Author: Whelan, F.
Stead, J.A.
Shkumatov, A.V.
Svergun, D.I.
Sanders, C.M.
Antson, A.A.
Citation: Nucleic Acids Research, 2012; 40(5):2271-2283
Publisher: Oxford University Press
Issue Date: 2012
ISSN: 0305-1048
Statement of
Fiona Whelan, Jonathan A. Stead, Alexander V. Shkumatov, Dmitri I. Svergun, Cyril M. Sanders, Alfred A. Antson
Abstract: The mechanism of DNA translocation by papillomavirus E1 and polyomavirus LTag hexameric helicases involves consecutive remodelling of subunit-subunit interactions around the hexameric ring. Our biochemical analysis of E1 helicase demonstrates that a 26-residue C-terminal segment is critical for maintaining the hexameric assembly. As this segment was not resolved in previous crystallographic analysis of E1 and LTag hexameric helicases, we determined the solution structure of the intact hexameric E1 helicase by Small Angle X-ray Scattering. We find that the C-terminal segment is flexible and occupies a cleft between adjacent subunits in the ring. Electrostatic potential calculations indicate that the negatively charged C-terminus can bridge the positive electrostatic potentials of adjacent subunits. Our observations support a model in which the C-terminal peptide serves as a flexible 'brace' maintaining the oligomeric state during conformational changes associated with ATP hydrolysis. We argue that these interactions impart processivity to DNA unwinding. Sequence and disorder analysis suggest that this mechanism of hexamer stabilization would be conserved among papillomavirus E1 and polyomavirus LTag hexameric helicases.
Keywords: DNA Helicases
DNA-Binding Proteins
Protein Subunits
Viral Proteins
X-Ray Diffraction
Sequence Deletion
Amino Acid Sequence
Conserved Sequence
Protein Structure, Tertiary
Models, Molecular
Molecular Sequence Data
Scattering, Small Angle
Protein Multimerization
Static Electricity
Rights: The Author(s) 2011. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
DOI: 10.1093/nar/gkr906
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Appears in Collections:Aurora harvest 4
Genetics publications

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