Solution structure of DFF40 and DFF45 N-terminal domain complex and mutual chaperone activity of DFF40 and DFF45

Proceedings of the National Academy of Sciences of the United States of America - Tập 98 Số 11 - Trang 6051-6055 - 2001
Pei Zhou1, Alexey A. Lugovskoy1, J S McCarty1, Peng Li1, Gerhard Wagner1
1Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115; Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, MA 02138; and Laboratory for Apoptosis Regulation, Institute of Molecular and Cell Biology, 30 Medical Drive, Singapore 117609, Singapore

Tóm tắt

Apoptotic DNA fragmentation is mediated by a caspase-activated DNA fragmentation factor (DFF)40. Expression and folding of DFF40 require the presence of DFF45, which also acts as a nuclease inhibitor before DFF40 activation by execution caspases. The N-terminal domains (NTDs) of both proteins are homologous, and their interaction plays a key role in the proper functioning of this two-component system. Here we report that the NTD of DFF45 alone is unstructured in solution, and its folding is induced upon binding to DFF40 NTD. Therefore, folding of both proteins regulates the formation of the DFF40/DFF45 complex. The solution structure of the heterodimeric complex between NTDs of DFF40 and DFF45 reported here shows that the mutual chaperoning includes the formation of an extensive network of intermolecular interactions that bury a hydrophobic cluster inside the interface, surrounded by intermolecular salt bridges.

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Thông tin xuất bản

Proceedings of the National Academy of Sciences of the United States of America

Tập 98 Số 11

6051-6055

Thông tin tác giả