Molecular basis for the selective recognition and ubiquitination of centromeric histone H3 by yeast E3 ligase Psh1 |
| |
| Institution: | 1. National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China;2. University of Chinese Academy of Sciences, Beijing 100089, China;1. Department of Health Sciences, Center on Autoimmune and Allergic Diseases (CAAD), UPO, University of Eastern Piedmont, A. Avogadro, Novara 28100, Italy;2. Consorzio Interuniversitario di Biotecnologie (CIB), Trieste 34149, Italy;3. Laboratory of Human Genetics of Neurological Disorders, Institute of Experimental Neurology, Division of Neurosciences, IRCCS San Raffaele Scientific Institute, Milan 20132, Italy;4. National Research Council of Italy, Institute for Biomedical Technologies, Segrate, Milan 20090, Italy;5. Department of Genetic Medicine and Development (GEDEV), Faculty of Medicine, University of Geneva Medical School, Geneva 1211, Switzerland;6. Department of Informatics, Systems and Communications (DISCo), University of Milano-Bicocca, Milan 20126, Italy;7. MS Centre, SCDU Neurology, AOU Maggiore della Carità, Novara 28100, Italy;8. Department of Translational Medicine, Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Eastern Piedmont, Novara, Avogadro University, Novara 28100, Italy;9. Neuroscience Institute Cavalieri Ottolenghi, Orbassano, Turin 10043, Italy;10. Neurobiology Unit, Neurology - CReSM (Regional Referring Center of Multiple Sclerosis), AOU San Luigi Gonzaga, Orbassano, Turin 10043, Italy;11. Department of Neuroscience ‘Rita Levi Montalcini’, University of Turin, Turin 10126, Italy;12. Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, Verona 37134, Italy;13. UO Neurologia Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia 71013, Italy;14. Centro Recupero e Rieducazione Funzionale “Mons L Novarese”, Moncrivello (VC) 13040, Italy;15. Department of Neurology, IRCCS San Raffaele Scientific Institute, Milan 20132, Italy;p. Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan 20132, Italy;q. Vita-Salute San Raffaele University, Milan 20138, Italy;r. Neurophysiology Unit, IRCCS San Raffaele Scientific Institute, Milan 20138, Italy;s. Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan, Milan 20122, Italy;t. Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Neurology Unit and MS Center, Milan 20122, Italy;1. State Key Laboratory of Cotton Biology, Institute of Cotton Research, Chinese Academy of Agricultural Sciences, Anyang, Henan 455000, China;2. School of Agricultural Sciences, Zhengzhou University, Zhengzhou, Henan 450001, China;3. Cotton Research Institute, Ayub Agricultural Research Institute, Multan 60000, Pakistan;4. Research Base, State Key Laboratory of Cotton Biology, Zhengzhou University, Zhengzhou, Henan 450001, China;1. National Key Laboratory of Crop Genetic Improvement, National Center of Plant Gene Research (Wuhan), Huazhong Agricultural University, Wuhan 430070, China;2. Jiangsu Kingearth Seed Co., Ltd., Yangzhou 225012, China;1. Department of Cell Biology, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China;2. Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China |
| |
| Abstract: | Centromeres are chromosomal loci marked by histone variant Cen H3(centromeric histone H3) and essential for genomic stability and cell division. The budding yeast E3 ubiquitin ligase Psh1 selectively recognizes the yeast Cen H3(Cse4) for ubiquitination and controls the cellular level of Cse4 for proteolysis,but the underlying mechanism remains largely unknown. Here, we show that Psh1 uses a Cse4-binding domain(CBD, residues 1-211) to interact with Cse4-H4 instead of H3-H4, yielding a dissociation constant(K_d) of 27 nM. Psh1 recognizes Cse4-specific residues in the L1 loop and a2 helix to ensure Cse4 binding and ubiquitination. We map the Psh1-binding region of Cse4-H4 and identify a wide range of Cse4-specific residues required for the Psh1-mediated Cse4 recognition and ubiquitination. Further analyses reveal that histone chaperone Scm3 can impair Cse4 ubiquitination by abrogating Psh1-Cse4 binding. Together, our study reveals a novel Cse4-binding mode distinct from those of known Cen H3 chaperones and elucidates the mechanism by which Scm3 competes with Psh1 for Cse4 binding. |
| |
| Keywords: | Cse4 CENP-A Psh1 Scm3 Selective recognition Ubiquitination |
| 本文献已被 CNKI ScienceDirect 等数据库收录！ |
|
