Structures of BCL-2 in complex with venetoclax reveal the molecular basis of resistance mutations
Richard W Birkinshaw, Jia-nan Gong, Cindy S Luo, Daisy Lio, Christine A White, Mary Ann Anderson, Piers Blombery, Guillaume Lessene, Ian J Majewski, Rachel Thijssen, Andrew W Roberts, David CS Huang, Peter M Colman, Peter E Czabotar
Nature Communications | NATURE PUBLISHING GROUP | Published : 2019
Awarded by NHMRC
Awarded by Leukemia and Lymphoma Society
Awarded by Cancer Council of Victoria
Research in the authors' laboratory is supported by NHMRC project grants (1059331 and 1079706), program grants (11131233 DCSH, PMC; 1113577 AWR) and fellowships (1156024 DCSH, 1079560 AWR, 1116934 PMC, 1079700 PEC), the Leukemia and Lymphoma Society (SCOR 7015-18 and Fellowship 5467-18 to RT), the Victorian Cancer Agency (Fellowship to IJM), project support from The Cancer Council of Victoria (Project 1124178 to IJM), the Victorian State Government Operational Infrastructure Support, and the Australian Government NHMRC IRIISS. This research was undertaken in part using the MX2 beamline at the Australian Synchrotron, part of ANSTO, and made use of the Australian Cancer Research Foundation (ACRF) detector. The authors would like to thank Yan-Hong Tan for technical assistance, Dr W. Douglas Fairlie and Dr Erina Lee for providing BCL-2 plasmid DNA and the Collaborative Crystallisation Centre (C3, CSIRO) for crystallisation screening. We would also like to thank Wayne Fairbrother for discussions related to the manuscript. Finally the authors would like to thank the following cats and their owners for donating their naturally shedded whiskers for crystallisation seeding experiments: Tilly, Boris, Patsy and Snoop Catty Cat.