Líffræðifélag Íslands - biologia.is
Líffræðiráðstefnan 2019
Erindi/veggspjald / Talk/poster V74
Höfundar / Authors: Pétur O. Heidarsson (1,2), Davide Mercadante (1), Madeleine Borgia (1), Alessandro Borgia (1), Andrea Sottini (1), Sinan Kilic (3), Daniel Nettels (1), Beat Fierz (3), Robert Best (4), Benjamin Schuler (1)
Starfsvettvangur / Affiliations: 1. Department of Biochemistry, University of Zurich, Wintherthurerstrasse 190, 8057 Zurich, Switzerland. 2. Department of Biochemistry, Science Institute, University of Iceland, Reykjavík, Iceland. 3. Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland. 4. Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0520, USA.
Kynnir / Presenter: Pétur Orri Heiðarsson
Proteins with highly charged disordered regions are abundant in the nucleus, and many of them interact with nucleic acids and control key processes such as transcription. The underlying mechanisms and functional benefits conferred by protein disorder, however, have remained largely unclear. Here we show that disorder facilitates remarkable mechanisms of regulation by molecular competition. Single-molecule experiments demonstrate that the human linker histone H1 binds to the nucleosome with ultra-high affinity. However, the pronounced dynamics of the positively charged disordered regions of H1 persist on the nucleosome and facilitate the interaction with the highly negatively charged and disordered histone chaperone prothymosin α. Consequently, prothymosin α can efficiently invade the H1-nucleosome complex and displace H1 via competitive substitution. By combining experiments and simulations, we establish a molecular model that rationalizes this process kinetically and structurally. Given the abundance of charged disordered regions in the nuclear proteome, such mechanisms may be widespread in cellular regulation.