Total chemical synthesis of the phosphorylated p62 UBA domain reveals that Ser407Pi but not Ser403Pi enhances ubiquitin binding

2020 ◽  
Vol 18 (42) ◽  
pp. 8709-8715
Author(s):  
Ling Xu ◽  
Yan Zhang ◽  
Yi-Ming Li ◽  
Xian-Fu Lu
Keyword(s):  
Chemical Synthesis ◽  
Binding Affinity ◽  
Ubiquitin Binding ◽  
Uba Domain

Based on total chemical synthesis we prepared four types of phosphorylated p62 UBAs and found that phosphorylation at S407 but not at S403 enhanced the binding affinity between UBA and Ub.

scholarly journals Coordination of Hpr1 and Ubiquitin Binding by the UBA Domain of the mRNA Export Factor Mex67

2007 ◽  
Vol 18 (7) ◽  
pp. 2561-2568 ◽  
Author(s):  
Maria Hobeika ◽  
Christoph Brockmann ◽  
Nahid Iglesias ◽  
Carole Gwizdek ◽  
David Neuhaus ◽  
...  
Keyword(s):  
Substrate Specificity ◽  
Conformational Change ◽  
Nuclear Export ◽  
Transcription Elongation ◽  
Mrna Export ◽  
Molecular Switch ◽  
Ubiquitin Binding ◽  
Uba Domain ◽  
Nuclear Export Receptor

The ubiquitin-associated (UBA) domain of the mRNA nuclear export receptor Mex67 helps in coordinating transcription elongation and nuclear export by interacting both with ubiquitin conjugates and specific targets, such as Hpr1, a component of the THO complex. Here, we analyzed substrate specificity and ubiquitin selectivity of the Mex67 UBA domain. UBA-Mex67 is formed by three helices arranged in a classical UBA fold plus a fourth helix, H4. Deletion or mutation of helix H4 strengthens the interaction between UBA-Mex67 and ubiquitin, but it decreases its affinity for Hpr1. Interaction with Hpr1 is required for Mex67 UBA domain to bind polyubiquitin, possibly by inducing an H4-dependent conformational change. In vivo, deletion of helix H4 reduces cotranscriptional recruitment of Mex67 on activated genes, and it also shows an mRNA export defect. Based on these results, we propose that H4 functions as a molecular switch that coordinates the interaction of Mex67 with ubiquitin bound to specific substrates, defines the selectivity of the Mex67 UBA domain for polyubiquitin, and prevents its binding to nonspecific substrates.

scholarly journals Aptamer-modified nanomaterials: principles and applications

2016 ◽  
Vol 18 (1-2) ◽  
Author(s):  
Katharina Urmann ◽  
Julia Modrejewski ◽  
Thomas Scheper ◽  
Johanna-G. Walter
Keyword(s):  
Chemical Synthesis ◽  
Binding Affinity ◽  
Nanostructured Materials ◽  
Nanostructured Material ◽  
Solid Support ◽  
Binding Properties ◽  
Promising Alternative ◽  
Nanostructured Surfaces ◽  
High Affinity

AbstractAptamers are promising alternative binders that can substitute antibodies in various applications. Due to the advantages of aptamers, namely their high affinity, specificity and stability, along with the benefits originating from the chemical synthesis of aptamers, they have attracted attention in various applications including their use on nanostructured material. This necessitates the immobilization of aptamers on a solid support. Since aptamer immobilization may interfere with its binding properties, the immobilization of aptamers has to be investigated and optimized. Within this review, we give general insights into the principles and factors controlling the binding affinity of immobilized aptamers. Specific features of aptamer immobilization on nanostructured surfaces and nanoparticles are highlighted and a brief overview of applications of aptamer-modified nanostructured materials is given.

scholarly journals N-terminal engineering of amyloid-β-binding Affibody molecules yields improved chemical synthesis and higher binding affinity

2010 ◽  
Vol 19 (12) ◽  
pp. 2319-2329 ◽  
Author(s):  
Joel Lindgren ◽  
Anna Wahlström ◽  
Jens Danielsson ◽  
Natalia Markova ◽  
Caroline Ekblad ◽  
...  
Keyword(s):  
Chemical Synthesis ◽  
Binding Affinity ◽  
Amyloid Β ◽  
Affibody Molecules

Chemical Synthesis of Diubiquitin-Based Photoaffinity Probes for Selectively Profiling Ubiquitin-Binding Proteins

2017 ◽  
Vol 129 (10) ◽  
pp. 2788-2792 ◽  
Author(s):  
Jun Liang ◽  
Lin Zhang ◽  
Xiang-Long Tan ◽  
Yun-Kun Qi ◽  
Shan Feng ◽  
...  
Keyword(s):  
Chemical Synthesis ◽  
Binding Proteins ◽  
Ubiquitin Binding ◽  
Photoaffinity Probes

The chemical synthesis and binding affinity to the EGF receptor of the EGF-like domain of heparin-binding EGF-like growth factor (HB-EGF)

2003 ◽  
Vol 9 (4) ◽  
pp. 244-250 ◽  
Author(s):  
Song Yub Shin ◽  
Tetsuo Yokoyama ◽  
Takato Takenouchi ◽  
Eisuke Munekata
Keyword(s):  
Growth Factor ◽  
Chemical Synthesis ◽  
Binding Affinity ◽  
Egf Receptor ◽  
Heparin Binding

scholarly journals Oxygen-dependent asparagine hydroxylation of the ubiquitin-associated (UBA) domain in Cezanne regulates ubiquitin binding

2020 ◽  
Vol 295 (8) ◽  
pp. 2160-2174 ◽  
Author(s):  
Julia Mader ◽  
Jessica Huber ◽  
Florian Bonn ◽  
Volker Dötsch ◽  
Vladimir V. Rogov ◽  
...  
Keyword(s):  
Catalytic Activity ◽  
Signaling Pathways ◽  
Posttranslational Modification ◽  
Regulatory Domain ◽  
Cellular Functions ◽  
Ubiquitin Chain ◽  
Ubiquitin Binding ◽  
Uba Domain ◽  
Ubiquitin Binding Domain

Deubiquitinases (DUBs) are vital for the regulation of ubiquitin signals, and both catalytic activity of and target recruitment by DUBs need to be tightly controlled. Here, we identify asparagine hydroxylation as a novel posttranslational modification involved in the regulation of Cezanne (also known as OTU domain–containing protein 7B (OTUD7B)), a DUB that controls key cellular functions and signaling pathways. We demonstrate that Cezanne is a substrate for factor inhibiting HIF1 (FIH1)- and oxygen-dependent asparagine hydroxylation. We found that FIH1 modifies Asn35 within the uncharacterized N-terminal ubiquitin-associated (UBA)-like domain of Cezanne (UBACez), which lacks conserved UBA domain properties. We show that UBACez binds Lys11-, Lys48-, Lys63-, and Met1-linked ubiquitin chains in vitro, establishing UBACez as a functional ubiquitin-binding domain. Our findings also reveal that the interaction of UBACez with ubiquitin is mediated via a noncanonical surface and that hydroxylation of Asn35 inhibits ubiquitin binding. Recently, it has been suggested that Cezanne recruitment to specific target proteins depends on UBACez. Our results indicate that UBACez can indeed fulfill this role as regulatory domain by binding various ubiquitin chain types. They also uncover that this interaction with ubiquitin, and thus with modified substrates, can be modulated by oxygen-dependent asparagine hydroxylation, suggesting that Cezanne is regulated by oxygen levels.

Sign in / Sign up

Export Citation Format

Share Document