Structures of heat shock factor trimers bound to DNA

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 - Copyright: © 2021 Institute of Biophysics, Chinese Academy of Sciences.

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.

KW - Molecular Structure

KW - Structural biology

KW - Protein structure aspects

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 -