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Full-Text Articles in Life Sciences
Hemi-Methylated Dna Regulates Dna Methylation Inheritance Through Allosteric Activation Of H3 Ubiquitylation By Uhrf1, Joseph S. Harrison, Evan M. Cornett, Dennis Goldfarb, Paul A. Darosa, Zimeng M. Li, Feng Yan, Bradley M. Dickson, Angela H. Guo, Daniel V. Cantu, Lilia Kaustov, Peter J. Brown, Cheryl H. Arrowsmith, Dorothy A. Erie, Michael B. Major, Rachel E. Klevit, Krzysztof Krajewski, Brian Kuhlman, Brian D. Strahl, Scott B. Rothbart
Hemi-Methylated Dna Regulates Dna Methylation Inheritance Through Allosteric Activation Of H3 Ubiquitylation By Uhrf1, Joseph S. Harrison, Evan M. Cornett, Dennis Goldfarb, Paul A. Darosa, Zimeng M. Li, Feng Yan, Bradley M. Dickson, Angela H. Guo, Daniel V. Cantu, Lilia Kaustov, Peter J. Brown, Cheryl H. Arrowsmith, Dorothy A. Erie, Michael B. Major, Rachel E. Klevit, Krzysztof Krajewski, Brian Kuhlman, Brian D. Strahl, Scott B. Rothbart
College of the Pacific Faculty Articles
The epigenetic inheritance of DNA methylation requires UHRF1, a histone- and DNA-binding RING E3 ubiquitin ligase that recruits DNMT1 to sites of newly replicated DNA through ubiquitylation of histone H3. UHRF1 binds DNA with selectivity towards hemi-methylated CpGs (HeDNA); however, the contribution of HeDNA sensing to UHRF1 function remains elusive. Here, we reveal that the interaction of UHRF1 with HeDNA is required for DNA methylation but is dispensable for chromatin interaction, which is governed by reciprocal positive cooperativity between the UHRF1 histone- and DNA-binding domains. HeDNA recognition activates UHRF1 ubiquitylation towards multiple lysines on the H3 tail adjacent to the …
Mechanism Of Lysine 48 Selectivity During Polyubiquitin Chain Formation By The Ube2r1/2 Ubiquitin-Conjugating Enzyme, Spencer Hill, Joseph S. Harrison, Steven M. Lewis, Brian Kuhlman, Gary Kleiger
Mechanism Of Lysine 48 Selectivity During Polyubiquitin Chain Formation By The Ube2r1/2 Ubiquitin-Conjugating Enzyme, Spencer Hill, Joseph S. Harrison, Steven M. Lewis, Brian Kuhlman, Gary Kleiger
College of the Pacific Faculty Articles
Lysine selectivity is of critical importance during polyubiquitin chain formation because the identity of the lysine controls the biological outcome. Ubiquitins are covalently linked in polyubiquitin chains through one of seven lysine residues on its surface and the C terminus of adjacent protomers. Lys 48-linked polyubiquitin chains signal for protein degradation; however, the structural basis for Lys 48 selectivity remains largely unknown. The ubiquitin-conjugating enzyme Ube2R1/2 has exquisite specificity for Lys 48, and computational docking of Ube2R1/2 and ubiquitin predicts that Lys 48 is guided to the active site through a key electrostatic interaction between Arg 54 on ubiquitin and …
An Allosteric Interaction Links Usp7 To Deubiquitination And Chromatin Targeting Of Uhrf1, Zhi-Min Zhang, Scott B. Rothbart, David F. Allison, Qian Cai, Joseph S. Harrison, Lin Li, Yinsheng Wang, Brian D. Strahl, Gang Greg Wang, Jikui Song
An Allosteric Interaction Links Usp7 To Deubiquitination And Chromatin Targeting Of Uhrf1, Zhi-Min Zhang, Scott B. Rothbart, David F. Allison, Qian Cai, Joseph S. Harrison, Lin Li, Yinsheng Wang, Brian D. Strahl, Gang Greg Wang, Jikui Song
College of the Pacific Faculty Articles
The protein stability and chromatin functions of UHRF1 (ubiquitin-like, containing PHD and RING finger domains, 1) are regulated in a cell-cycle-dependent manner. We report a structural characterization of the complex between UHRF1 and the deubiquitinase USP7. The first two UBL domains of USP7 bind to the polybasic region (PBR) of UHRF1, and this interaction is required for the USP7-mediated deubiquitination of UHRF1. Importantly, we find that the USP7-binding site of the UHRF1 PBR overlaps with the region engaging in an intramolecular interaction with the N-terminal tandem Tudor domain (TTD). We show that the USP7-UHRF1 interaction perturbs the TTD-PBR interaction of …
Side Chain Requirements For Affinity And Specificity In D5, An Hiv-1 Antibody Derived From The Vh1-69 Germline Segment, Alex Stewart, Joseph S. Harrison, Lauren K. Regula, Jonathan R. Lai
Side Chain Requirements For Affinity And Specificity In D5, An Hiv-1 Antibody Derived From The Vh1-69 Germline Segment, Alex Stewart, Joseph S. Harrison, Lauren K. Regula, Jonathan R. Lai
College of the Pacific Faculty Articles
BACKGROUND: Analysis of factors contributing to high affinity antibody-protein interactions provides insight into natural antibody evolution, and guides the design of antibodies with new or enhanced function. We previously studied the interaction between antibody D5 and its target, a designed protein based on HIV-1 gp41 known as 5-Helix, as a model system [Da Silva, G. F.; Harrison, J. S.; Lai, J. R., Biochemistry, 2010, 49, 5464-5472]. Antibody D5 represents an interesting case study because it is derived from the VH1-69 germline segment; this germline segment is characterized by a hydrophobic second heavy chain complementarity determining region (HCDR2) that constitutes the …