TY - JOUR
T1 - Structures of heat shock factor trimers bound to DNA
AU - Feng, Na
AU - Feng, Han
AU - Wang, Sheng
AU - Punekar, Avinash S
AU - Ladenstein, Rudolf
AU - Wang, Da-Cheng
AU - Zhang, Qinghua
AU - Ding, Jingjin
AU - Liu, Wei
N1 - We would like to thank the staff of BL18U1 and BL19U1 beamlines at National Center for Protein Sciences Shanghai and Shanghai Synchrotron Radiation Facility, Shanghai, People's Republic of China, for assistance during data collection. This work was supported by the National Natural Science Foundation of China ( 31270788 ), National Key Research and Development Programs of China ( 2017YFA0504000 ) the Special Program of Planned Parenthood ( 19JSZ02 ), the Excellent Young Scholar Program of the National Natural Science Foundation of China ( 81922043 ) the program Youth Innovation Promotion Association CAS 692 ( 2017127 ), Key Projects from Chongqing Science and Technology Commission ( cstc2018jscxmszdX0020 ).
PY - 2021/9/24
Y1 - 2021/9/24
N2 - Heat shock factor 1 (HSF1) and 2 (HSF2) play distinct but overlapping regulatory roles in maintaining cellular proteostasis or mediating cell differentiation and development. Upon activation, both HSFs trimerize and bind to heat shock elements (HSEs) present in the promoter region of target genes. Despite structural insights gained from recent studies, structures reflecting the physiological architecture of this transcriptional machinery remains to be determined. Here, we present co-crystal structures of human HSF1 and HSF2 trimers bound to DNA, which reveal a triangular arrangement of the three DNA-binding domains (DBDs) with protein-protein interactions largely mediated by the wing domain. Two structural properties, different flexibility of the wing domain and local DNA conformational changes induced by HSF binding, seem likely to contribute to the subtle differential specificity between HSF1 and HSF2. Besides, two more structures showing DBDs bound to "two-site" head-to-head HSEs were determined as additions to the published tail-to-tail dimer-binding structures.
AB - Heat shock factor 1 (HSF1) and 2 (HSF2) play distinct but overlapping regulatory roles in maintaining cellular proteostasis or mediating cell differentiation and development. Upon activation, both HSFs trimerize and bind to heat shock elements (HSEs) present in the promoter region of target genes. Despite structural insights gained from recent studies, structures reflecting the physiological architecture of this transcriptional machinery remains to be determined. Here, we present co-crystal structures of human HSF1 and HSF2 trimers bound to DNA, which reveal a triangular arrangement of the three DNA-binding domains (DBDs) with protein-protein interactions largely mediated by the wing domain. Two structural properties, different flexibility of the wing domain and local DNA conformational changes induced by HSF binding, seem likely to contribute to the subtle differential specificity between HSF1 and HSF2. Besides, two more structures showing DBDs bound to "two-site" head-to-head HSEs were determined as additions to the published tail-to-tail dimer-binding structures.
U2 - 10.1016/j.isci.2021.102951
DO - 10.1016/j.isci.2021.102951
M3 - Article
C2 - 34458700
SN - 2589-0042
VL - 24
JO - iScience
JF - iScience
IS - 9
M1 - 102951
ER -