In this section
@article{Gao:2025:10.1073/pnas.2425868122,
author = {Gao, F and Ye, F and Buck, M and Zhang, X},
doi = {10.1073/pnas.2425868122},
journal = {Proceedings of the National Academy of Sciences},
title = {Subunit specialization in AAA+ proteins and substrate unfolding during transcription complex remodeling},
url = {http://dx.doi.org/10.1073/pnas.2425868122},
volume = {122},
year = {2025}
}
TY - JOUR
AB - Bacterial RNA polymerase (RNAP) is a multisubunit enzyme that copies DNA into RNA in a process known as transcription. Bacteria use σ factors to recruit RNAP to promoter regions of genes that need to be transcribed, with 60% bacteria containing at least one specialized σ factor, σ54. σ54 recruits RNAP to promoters of genes associated with stress responses and forms a stable closed complex that does not spontaneously isomerize to the open state where promoter DNA is melted out and competent for transcription. The σ54-mediated open complex formation requires specific AAA+ proteins (ATPases Associated with diverse cellular Activities) known as bacterial enhancer-binding proteins (bEBPs). We have now obtained structures of new intermediate states of bEBP-bound complexes during transcription initiation, which elucidate the mechanism of DNA melting driven by ATPase activity of bEBPs and suggest a mechanistic model that couples the Adenosine triphosphate (ATP) hydrolysis cycle within the bEBP hexamer with σ54 unfolding. Our data reveal that bEBP forms a nonplanar hexamer with the hydrolysis-ready subunit located at the furthest/highest point of the spiral hexamer relative to the RNAP. ATP hydrolysis induces conformational changes in bEBP that drives a vectoral transiting of the regulatory N terminus of σ54 into the bEBP hexamer central pore causing the partial unfolding of σ54, while forming specific bEBP contacts with promoter DNA. Furthermore, our data suggest a mechanism of the bEBP AAA+ protein that is distinct from the hand-over-hand mechanism proposed for many other AAA+ proteins, highlighting the versatile mechanisms utilized by the large protein family.
AU - Gao,F
AU - Ye,F
AU - Buck,M
AU - Zhang,X
DO - 10.1073/pnas.2425868122
PY - 2025///
SN - 0027-8424
TI - Subunit specialization in AAA+ proteins and substrate unfolding during transcription complex remodeling
T2 - Proceedings of the National Academy of Sciences
UR - http://dx.doi.org/10.1073/pnas.2425868122
UR - https://doi.org/10.1073/pnas.2425868122
VL - 122
ER -
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