Structural and Biochemical Analysis of Full-Length Huntingtin Illuminate the Impact of the Polyglutamine Region
Event details
| Date | 09.06.2017 |
| Hour | 15:00 |
| Speaker | Prof. Ji-Joon Song, KAIST, Daejeon (KOR) |
| Location | |
| Category | Conferences - Seminars |
BIOENGINEERING SEMINAR
Abstract:
The polyglutamine expansion in huntingtin protein causes Huntington’s disease but it remains unclear how this mutation alters full-length huntingtin structure and function. Here, we investigated the effects of the polyglutamine tract expansion on bio-physicochemical properties of huntingtin. We analyzed the 3D structures and the intra-molecular interactions of Q23- and Q78-huntingtin by negatively-stained electron microscopy and cross-linking mass spectrometry respectively, indicating that huntingtin adopts a spherical shape with a large central cavity and folds back to enable many intra-molecular interactions. Using a panel of highly purified human recombinant huntingtins with polyglutamine lengths of 2, 23, 46, 67 and 78 residues, we found that the polyglutamine expansion apparently increases the α-helicity of huntingtin, and alters huntingtin phosphorylation sites to modulate huntingtin’s function of stimulating PRC2 histone methyltransferase activity. Our works provide the first glimpse into the structure of full-length huntingtin and reveal the effect of polyglutamine expansion on full-length huntingtin phosphorylation and function.
Bio:
2009–2013 Assistant Professor
Department of Biological Sciences
KAIST, Daejeon, South Korea
2005–2009 Postdoctoral Research Fellow, Jane Coffin Childs Fellow
Department of Molecular Biology and Genetics
Massachusetts General Hospital, Harvard Medical School, MA, USA.
2001–2005 Doctoral Student
Watson School of Biological Sciences
Cold Spring Harbor Laboratory, NY, USA
Abstract:
The polyglutamine expansion in huntingtin protein causes Huntington’s disease but it remains unclear how this mutation alters full-length huntingtin structure and function. Here, we investigated the effects of the polyglutamine tract expansion on bio-physicochemical properties of huntingtin. We analyzed the 3D structures and the intra-molecular interactions of Q23- and Q78-huntingtin by negatively-stained electron microscopy and cross-linking mass spectrometry respectively, indicating that huntingtin adopts a spherical shape with a large central cavity and folds back to enable many intra-molecular interactions. Using a panel of highly purified human recombinant huntingtins with polyglutamine lengths of 2, 23, 46, 67 and 78 residues, we found that the polyglutamine expansion apparently increases the α-helicity of huntingtin, and alters huntingtin phosphorylation sites to modulate huntingtin’s function of stimulating PRC2 histone methyltransferase activity. Our works provide the first glimpse into the structure of full-length huntingtin and reveal the effect of polyglutamine expansion on full-length huntingtin phosphorylation and function.
Bio:
2009–2013 Assistant Professor
Department of Biological Sciences
KAIST, Daejeon, South Korea
2005–2009 Postdoctoral Research Fellow, Jane Coffin Childs Fellow
Department of Molecular Biology and Genetics
Massachusetts General Hospital, Harvard Medical School, MA, USA.
2001–2005 Doctoral Student
Watson School of Biological Sciences
Cold Spring Harbor Laboratory, NY, USA
Practical information
- Informed public
- Free
Organizer
Contact
- Institute of Bioengineering (IBI, Dietrich REINHARD)