Communications Biology (Dec 2021)
Huntingtin structure is orchestrated by HAP40 and shows a polyglutamine expansion-specific interaction with exon 1
- Rachel J. Harding,
- Justin C. Deme,
- Johannes F. Hevler,
- Sem Tamara,
- Alexander Lemak,
- Jeffrey P. Cantle,
- Magdalena M. Szewczyk,
- Nola Begeja,
- Siobhan Goss,
- Xiaobing Zuo,
- Peter Loppnau,
- Alma Seitova,
- Ashley Hutchinson,
- Lixin Fan,
- Ray Truant,
- Matthieu Schapira,
- Jeffrey B. Carroll,
- Albert J. R. Heck,
- Susan M. Lea,
- Cheryl H. Arrowsmith
Affiliations
- Rachel J. Harding
- Structural Genomics Consortium, University of Toronto
- Justin C. Deme
- Sir William Dunn School of Pathology, University of Oxford
- Johannes F. Hevler
- Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute of Pharmaceutical Sciences, Utrecht University
- Sem Tamara
- Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute of Pharmaceutical Sciences, Utrecht University
- Alexander Lemak
- Princess Margaret Cancer Centre and Department of Medical Biophysics, University of Toronto
- Jeffrey P. Cantle
- Behavioral Neuroscience Program, Department of Psychology, Western Washington University
- Magdalena M. Szewczyk
- Structural Genomics Consortium, University of Toronto
- Nola Begeja
- Department of Biochemistry and Biomedical Sciences, McMaster University
- Siobhan Goss
- Department of Biochemistry and Biomedical Sciences, McMaster University
- Xiaobing Zuo
- X-ray Science Division, Argonne National Laboratory
- Peter Loppnau
- Structural Genomics Consortium, University of Toronto
- Alma Seitova
- Structural Genomics Consortium, University of Toronto
- Ashley Hutchinson
- Structural Genomics Consortium, University of Toronto
- Lixin Fan
- Basic Science Program, Frederick National Laboratory for Cancer Research, SAXS Core of NCI, National Institutes of Health
- Ray Truant
- Department of Biochemistry and Biomedical Sciences, McMaster University
- Matthieu Schapira
- Structural Genomics Consortium, University of Toronto
- Jeffrey B. Carroll
- Behavioral Neuroscience Program, Department of Psychology, Western Washington University
- Albert J. R. Heck
- Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute of Pharmaceutical Sciences, Utrecht University
- Susan M. Lea
- Sir William Dunn School of Pathology, University of Oxford
- Cheryl H. Arrowsmith
- Structural Genomics Consortium, University of Toronto
- DOI
- https://doi.org/10.1038/s42003-021-02895-4
- Journal volume & issue
-
Vol. 4,
no. 1
pp. 1 – 16
Abstract
Harding et al. present a biophysical and structural characterization of the complex between huntingtin (HTT) and HAP40 proteins. They show that the abundance of HAP40 is coupled with that of HTT and that there is greater conformational variety in the exon 1 of the mutant HTT than WT, important for the future drug discovery studies targeting Huntington’s disease.
