A Human Tumor Virus Recruits HSP70 Chaperone to Remodel Its Replisome on DNA
- 1University of Pittsburgh
Abstract
Human Merkel cell polyomavirus (MCV) large T (LT) protein functions as a replication helicase analogous to the cellular MCM complex but requires a second MCV protein, small T (sT), for efficient LT-initiated replication. Both LT and sT encode highly-conserved DnaJ domains that bind to the cellular refolding molecule, heat shock protein 70 (HSP70). Using single-molecule imaging and FRET, we find that sT recruits dimeric HSP70 to serve as a molecular bridge between sT and LT on DNA and that this complex facilitates remodeling LT into a functional double-hexameric helicase. Disruption of LT-HSP70-HSP70-sT interaction with HSP70 inhibitors or by mutations to the LT-sT DnaJ domains collapse the LT-HSP70-HSP70-sT complex, abolishing sT-enhanced LT dodecamerization and ATP-dependent DNA unwinding. Assembly of virus-free mammalian MCM3, MCM4 and MCM6 in nuclear extracts similarly recruits HSP70 to DNA suggesting that Hsp70 remodeling is used for efficient eukaryotic assembly of the multi-protein replication machinery.
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BibTeX
@misc{wan2026human,
title = {{A Human Tumor Virus Recruits HSP70 Chaperone to Remodel Its Replisome on DNA}},
author = {L. Wan and X. Li and P. Vittot and J. Brodsky and P. Wipf and P. S. Moore and Y. Chang},
howpublished = {bioRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.05.764654},
url = {https://www.biorxiv.org/content/10.64898/2026.11.05.764654v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - A Human Tumor Virus Recruits HSP70 Chaperone to Remodel Its Replisome on DNA
AU - L. Wan
AU - X. Li
AU - P. Vittot
AU - J. Brodsky
AU - P. Wipf
AU - P. S. Moore
AU - Y. Chang
PY - 2026
DA - 2026/11/05
PB - bioRxiv
DO - 10.64898/2026.11.05.764654
UR - https://www.biorxiv.org/content/10.64898/2026.11.05.764654v1
AB - Human Merkel cell polyomavirus (MCV) large T (LT) protein functions as a replication helicase analogous to the cellular MCM complex but requires a second MCV protein, small T (sT), for efficient LT-initiated replication. Both LT and sT encode highly-conserved DnaJ domains that bind to the cellular refolding molecule, heat shock protein 70 (HSP70). Using single-molecule imaging and FRET, we find that sT recruits dimeric HSP70 to serve as a molecular bridge between sT and LT on DNA and that this complex facilitates remodeling LT into a functional double-hexameric helicase. Disruption of LT-HSP70-HSP70-sT interaction with HSP70 inhibitors or by mutations to the LT-sT DnaJ domains collapse the LT-HSP70-HSP70-sT complex, abolishing sT-enhanced LT dodecamerization and ATP-dependent DNA unwinding. Assembly of virus-free mammalian MCM3, MCM4 and MCM6 in nuclear extracts similarly recruits HSP70 to DNA suggesting that Hsp70 remodeling is used for efficient eukaryotic assembly of the multi-protein replication machinery.
ER -