Structures of heat shock factor trimers bound to DNA
Na Feng,
Han Feng,
Sheng Wang,
Avinash S. Punekar,
Rudolf Ladenstein,
Da-Cheng Wang,
Qinghua Zhang,
Jingjin Ding,
Wei Liu
Affiliations
Na Feng
National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China
Han Feng
CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
Sheng Wang
College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China
Avinash S. Punekar
Department of Biosciences and Nutrition, Karolinska Institutet NEO, 14183 Huddinge, Sweden
Rudolf Ladenstein
Department of Biosciences and Nutrition, Karolinska Institutet NEO, 14183 Huddinge, Sweden
Da-Cheng Wang
National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
Qinghua Zhang
Department of Obstetrics and Gynecology, Daping Hospital, Army Medical University of PLA, Chongqing 400042, China; Corresponding author
Jingjin Ding
National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; Corresponding author
Wei Liu
Institute of Immunology, Army Medical University, Chongqing 400038, China; Corresponding author
Summary: 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.
