基本信息
浏览量:184
职业迁徙
个人简介
The Schulman lab studies the structural basis for post-translational modification by ubiquitin and ubiquitin-like proteins (Ubls). Post-translational covalent attachment of Ubls to protein targets is a primary eukaryotic regulatory mechanism. There are more than a dozen Ubls in higher eukaryotes—such as ubiquitin, NEDD8, ISG15, and SUMO—that covalently modify myriad substrates. The best understood function of a Ubl modification is ubiquitin-mediated proteasomal degradation. However, different Ubls alter the functions of their targets in different ways, such as by changing the target's subcellular localization, enzymatic activity, or interactions with other proteins or DNA. Moreover, defects in these pathways have been widely associated with diseases such as cancer, neurodegenerative disorders and viral infections.
Ubls are attached to protein targets by a series of molecular handoffs involving an E1 activating enzyme, an E2 conjugating enzyme (or Ubc), an E3 ligase, and the target. First, at the apex of each Ubl's cascade, a dedicated E1 enzyme selects its Ubl and catalyzes adenylation of the Ubl’s C-terminus. The E1 then forms a thioester intermediate between the E1's catalytic cysteine and the Ubl's C terminus, and ultimately catalyzes Ubl transfer to an E2's catalytic cysteine to generate a thioester-linked E2~Ubl covalent product. The E2~Ubl complex typically associates with an E3, which facilitates transfer of the Ubl to the target.
We believe that determining the mechanisms by which enzymes transfer Ubls will be of broad importance, much like studies of protein kinases have influenced our knowledge of signaling pathways and their roles in diseases. Toward this end, the goals of our research are (1) to understand the basic enzymatic mechanisms underlying Ubl attachment to targets, (2) to understand how Ubls are attached selectively, and (3) to understand mechanisms by which Ubl covalent attachment can change enzyme and target function.
Research Interests
Post-translational modification by ubiquitin-like proteins
Ubiquitin-mediated proteolysis
Protein design to understand cell cycle control
Ubls are attached to protein targets by a series of molecular handoffs involving an E1 activating enzyme, an E2 conjugating enzyme (or Ubc), an E3 ligase, and the target. First, at the apex of each Ubl's cascade, a dedicated E1 enzyme selects its Ubl and catalyzes adenylation of the Ubl’s C-terminus. The E1 then forms a thioester intermediate between the E1's catalytic cysteine and the Ubl's C terminus, and ultimately catalyzes Ubl transfer to an E2's catalytic cysteine to generate a thioester-linked E2~Ubl covalent product. The E2~Ubl complex typically associates with an E3, which facilitates transfer of the Ubl to the target.
We believe that determining the mechanisms by which enzymes transfer Ubls will be of broad importance, much like studies of protein kinases have influenced our knowledge of signaling pathways and their roles in diseases. Toward this end, the goals of our research are (1) to understand the basic enzymatic mechanisms underlying Ubl attachment to targets, (2) to understand how Ubls are attached selectively, and (3) to understand mechanisms by which Ubl covalent attachment can change enzyme and target function.
Research Interests
Post-translational modification by ubiquitin-like proteins
Ubiquitin-mediated proteolysis
Protein design to understand cell cycle control
研究兴趣
论文共 243 篇作者统计合作学者相似作者
按年份排序按引用量排序主题筛选期刊级别筛选合作者筛选合作机构筛选
时间
引用量
主题
期刊级别
合作者
合作机构
Laura A. Hehl,Daniel Horn-Ghetko,J. Rajan Prabu, Ronnald Vollrath, D. Tung Vu, David A. Pérez Berrocal,Monique P. C. Mulder, Gerbrand J. van der Heden van Noort,Brenda A. Schulman
Nature Chemical Biologyno. 2 (2024): 190-200
Jerry Li, Nicholas Purser, Joanna Liwocha,Daniel C. Scott, Holly A. Byers, Barbara Steigenberger,Spencer Hill, Ishita Tripathi-Giesgen,Trent Hinkle, Fynn M. Hansen, J. Rajan Prabu,Senthil K. Radhakrishnan,
Molecular Cell (2024)
J Wade Harper,Felix Kraus,Yuchen He,Sharan Swarup,Katherine A Overmyer, Johann Brenner,Cristina Capitanio,Anna Bieber,Annie Jen, Nicole M Nightingale, Benton J Anderson, Chan Lee,
crossref(2024)
J. Josephine Botsch, Roswitha Junker,Michele Sorgenfrei, Patricia P. Ogger, Luca Stier,Susanne von Gronau,Peter J. Murray,Markus A. Seeger,Brenda A. Schulman,Bastian Braeuning
Joanna Liwocha,Jerry Li, Nicholas Purser, Chutima Rattanasopa, Samuel Maiwald, David T. Krist,Daniel C. Scott, Barbara Steigenberger, J. Rajan Prabu,Brenda A. Schulman,Gary Kleiger
Nature Structural & Molecular Biologyno. 2 (2024): 378-389
Felix Kraus,Yuchen He,Sharan Swarup,Katherine A Overmyer,Yizhi Jiang, Johann Brenner,Cristina Capitanio,Anna Bieber,Annie Jen, Nicole M Nightingale, Benton J Anderson, Chan Lee,
bioRxiv : the preprint server for biology (2024)
Daniel Horn-Ghetko,Linus V. M. Hopf, Ishita Tripathi-Giesgen, Jiale Du,Sebastian Kostrhon, D. Tung Vu,Viola Beier,Barbara Steigenberger,J. Rajan Prabu, Luca Stier, Elias M. Bruss,Matthias Mann,
Nature Structural & Molecular Biology (2024)
Frank Adolf, Jiale Du,Ellen A Goodall,Richard M Walsh,Shaun Rawson, Susanne von Gronau,J Wade Harper,John Hanna,Brenda A Schulman
Daniel Horn-Ghetko,Linus V. M. Hopf, Ishita Tripathi-Giesgen, Jiale Du, Sebastian Kostrhon, D. Tung Vu, Viola Beier, Barbara Steigenberger, J. Rajan Prabu, Luca Stier, Elias M. Bruss, Matthias Mann,
加载更多
作者统计
合作学者
合作机构
D-Core
- 合作者
- 学生
- 导师
数据免责声明
页面数据均来自互联网公开来源、合作出版商和通过AI技术自动分析结果,我们不对页面数据的有效性、准确性、正确性、可靠性、完整性和及时性做出任何承诺和保证。若有疑问,可以通过电子邮件方式联系我们:report@aminer.cn