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Solution Conformations of Prototype Foamy Virus Integrase and Its Stable Synaptic Complex with U5 Viral DNA

Published

Author(s)

Kushol Gupta, Joseph E. Curtis, Susan N. Krueger, Young Hwang, Peter Cherepanov, Frederic Bushman, Gregory D. Van Duyne

Abstract

The recently determined crystal structures of prototype foamy virus integrase (PFV IN) in complex with viral DNA and target DNA reveal the first high-resolution insights into the nucleoprotein intermediates involved in retroviral integration. Using small-angle x-ray and neutron scattering (SAXS/SANS) in combination with analytical centrifugation and light scattering, we have determined the solution properties of the PFV IN alone and its stable synaptic complex (SSC) with U5 DNA and directly relate these properties to quaternary structural models derived from available crystal structures. PFV IN alone exists as a monomer in solution, and its structure is different from that observed in the crystallographic DNA-bound state. Our SAXS analysis suggests a quaternary model where the integrase samples a number of configurations of the N-terminal Domains (NTD-NED) and C0terminal Domains (CTD) that differ from their final DNA-bound state. We extend our analysis to include the stable synaptic complex formed between IN and U5 viral LTR oligonucleotide. The overall shape of this complex is consistent with the tetrameric assembly inferred from crystallographic symmetry and its quaternary structure is largely preserved in the presence of divalent ions and clinical stand transfer inhibitors. Using contrast variation methods, we have reconstructed the solution of the complex, locating distal domains unresolved by crystallography. These results together provide important insights into the complete quaternary arrangement of the retroviral intasome as it exists in solution.
Citation
Structure
Volume
20
Issue
11

Keywords

small-angle neutron scattering, protein, dna, protein-dna complex, retroviral integration

Citation

Gupta, K. , Curtis, J. , Krueger, S. , Hwang, Y. , Cherepanov, P. , Bushman, F. and Van Duyne, G. (2012), Solution Conformations of Prototype Foamy Virus Integrase and Its Stable Synaptic Complex with U5 Viral DNA, Structure, [online], https://doi.org/10.1016/j.str.2012.08.023 (Accessed February 18, 2025)

Issues

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Created November 1, 2012, Updated January 15, 2025