Nature Communications (Jun 2019)
Structural and functional consequences of the STAT5BN642H driver mutation
- Elvin D. de Araujo,
- Fettah Erdogan,
- Heidi A. Neubauer,
- Deniz Meneksedag-Erol,
- Pimyupa Manaswiyoungkul,
- Mohammad S. Eram,
- Hyuk-Soo Seo,
- Abdul K. Qadree,
- Johan Israelian,
- Anna Orlova,
- Tobias Suske,
- Ha T. T. Pham,
- Auke Boersma,
- Simone Tangermann,
- Lukas Kenner,
- Thomas Rülicke,
- Aiping Dong,
- Manimekalai Ravichandran,
- Peter J. Brown,
- Gerald F. Audette,
- Sarah Rauscher,
- Sirano Dhe-Paganon,
- Richard Moriggl,
- Patrick T. Gunning
Affiliations
- Elvin D. de Araujo
- Department of Chemical and Physical Sciences, University of Toronto Mississauga
- Fettah Erdogan
- Department of Chemical and Physical Sciences, University of Toronto Mississauga
- Heidi A. Neubauer
- Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna
- Deniz Meneksedag-Erol
- Department of Chemical and Physical Sciences, University of Toronto Mississauga
- Pimyupa Manaswiyoungkul
- Department of Chemical and Physical Sciences, University of Toronto Mississauga
- Mohammad S. Eram
- Dalriada Drug Discovery, University of Toronto Mississauga
- Hyuk-Soo Seo
- Department of Cancer Biology, Dana-Farber Cancer Institute
- Abdul K. Qadree
- Department of Chemical and Physical Sciences, University of Toronto Mississauga
- Johan Israelian
- Department of Chemical and Physical Sciences, University of Toronto Mississauga
- Anna Orlova
- Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna
- Tobias Suske
- Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna
- Ha T. T. Pham
- Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna
- Auke Boersma
- Institute of Laboratory Animal Science, University of Veterinary Medicine Vienna
- Simone Tangermann
- Unit of Laboratory Animal Pathology, University of Veterinary Medicine Vienna
- Lukas Kenner
- Ludwig Boltzmann Institute for Cancer Research
- Thomas Rülicke
- Institute of Laboratory Animal Science, University of Veterinary Medicine Vienna
- Aiping Dong
- Structural Genomics Consortium, University of Toronto
- Manimekalai Ravichandran
- Structural Genomics Consortium, University of Toronto
- Peter J. Brown
- Structural Genomics Consortium, University of Toronto
- Gerald F. Audette
- Department of Chemistry, York University
- Sarah Rauscher
- Department of Chemical and Physical Sciences, University of Toronto Mississauga
- Sirano Dhe-Paganon
- Department of Cancer Biology, Dana-Farber Cancer Institute
- Richard Moriggl
- Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna
- Patrick T. Gunning
- Department of Chemical and Physical Sciences, University of Toronto Mississauga
- DOI
- https://doi.org/10.1038/s41467-019-10422-7
- Journal volume & issue
-
Vol. 10,
no. 1
pp. 1 – 15
Abstract
Hyper-activated STAT5B and its disease-causing variants are of interest as cancer drug targets. Here the authors combine cell based studies, X-ray crystallography, biophysical experiments and MD simulations to structurally and functionally characterize the STAT5BN642H mutant found in aggressive T-cell leukemia and lymphomas and find that it has an increased affinity for self-dimerization.
