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Transient structure...
Transient structure and intrinsic disorder in the c-Myc transactivation domain and its effects on ligand binding
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- Andrésen, Cecilia (författare)
- Linköpings universitet,Molekylär Bioteknik,Tekniska högskolan
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- Helander, Sara (författare)
- Linköpings universitet,Molekylär Bioteknik,Tekniska högskolan
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- Lemak, Alexander (författare)
- Department of Medical Biophysics, University of Toronto, 101 College Street, Toronto, Ontario M5G 1L7, Canada
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visa fler...
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- Farès, Christophe (författare)
- Department of Medical Biophysics, University of Toronto, 101 College Street, Toronto, Ontario M5G 1L7, Canada
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- Csizmok, Veronika (författare)
- Molecular Structure and Function Program, Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada
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- Carlsson, Jonas (författare)
- Linköpings universitet,Molekylär Bioteknik,Tekniska högskolan
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- Penn, Linda Z. (författare)
- Department of Medical Biophysics, University of Toronto, 101 College Street, Toronto, Ontario M5G 1L7, Canada
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- Forman-Kay, Julie D. (författare)
- Molecular Structure and Function Program, Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada
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- Arrowsmith, Cheryl H. (författare)
- Department of Medical Biophysics, University of Toronto, 101 College Street, Toronto, Ontario M5G 1L7, Canada
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- Lundström, Patrik (författare)
- Linköpings universitet,Molekylär Bioteknik,Tekniska högskolan
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- Sunnerhagen, Maria (författare)
- Linköpings universitet,Molekylär Bioteknik,Tekniska högskolan
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(creator_code:org_t)
- Engelska.
- Relaterad länk:
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https://urn.kb.se/re...
Abstract
Ämnesord
Stäng
- The crucial role of c-Myc as an oncoprotein and as a key regulator of cell growth makes it essential to understand the molecular basis of c-Myc function. The transactivation domain of c-Myc coordinates a wealth of protein interactions involved in transformation, differentiation and apoptosis. We have characterized in detail the intrinsically disordered properties of c-Myc-1-88, where hierarchical phosphorylation of T58 and S62 regulates activation and destruction of the c-Myc protein. By NMR chemical shift analysis, relaxation measurements and NOE analysis, we show that both the MBI region (residues 45-65) and residues 22-33 are transiently structured regions, conserved also in other members of the Myc family. Binding of Bin1-SH3 to c-Myc-1-88 as assayed by NMR and SPR revealed primary binding to the S62 region, but also a dynamically disordered and multivalent complex in which intrinsic disorder of c-Myc-1-88 was retained while releasing transient intramolecular interactions. Our findings describe a novel mode of regulatory recognition of c-Myc that is in agreement with the increasingly recognized capability of intrinsically disordered regions to efficiently mediate transient interactions with a wide range of targets, with important implications towards understanding the unique multifaceted biological functions of c-Myc.
Nyckelord
- NATURAL SCIENCES
- NATURVETENSKAP
Publikations- och innehållstyp
- vet (ämneskategori)
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- Av författaren/redakt...
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Andrésen, Cecili ...
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Helander, Sara
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Lemak, Alexander
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Farès, Christoph ...
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Csizmok, Veronik ...
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Carlsson, Jonas
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visa fler...
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Penn, Linda Z.
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Forman-Kay, Juli ...
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Arrowsmith, Cher ...
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Lundström, Patri ...
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Sunnerhagen, Mar ...
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visa färre...
- Av lärosätet
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Linköpings universitet