7 results on '"SUTTON, ROGER"'
Search Results
2. Commentary on: Tolvaptan in Patients With Autosomal-Dominant Polycystic Kidney Disease
- Author
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Black, Peter and Sutton, Roger
- Published
- 2013
- Full Text
- View/download PDF
3. Kinetics of the Association/Dissociation Cycle of an ATP-binding Cassette Nucleotide-binding Domain.
- Author
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Zoghbi, Maria E., Fuson, Kerry L., Sutton, Roger B., and Altenberg, Guillermo A.
- Subjects
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BIOMOLECULES , *AMINO acids , *TRYPTOPHAN , *PROTEINS , *PUMPING machinery , *HYDROLYSIS - Abstract
Most ATP binding cassette (ABC) proteins are pumps that transport substrates across biological membranes using the energy of ATP hydrolysis. Functional ABC proteins have two nucleotide-binding domains (NBDs) that bind and hydrolyze ATP, but the molecular mechanism of nucleotide hydrolysis is unresolved. This is due in part to the limited kinetic information on NBD association and dissociation. Here, we show dimerization of a catalytically active NBD and follow in real time the association and dissociation of NBDs from the changes in fluorescence emission of a tryptophan strategically located at the center of the dimer interface. Spectroscopic and structural studies demonstrated that the tryptophan can be used as dimerization probe, and we showed that under hydrolysis conditions (millimolar MgATP), not only the dimer dissociation rate increases, but also the dimerization rate. Neither dimer formation or dissociation are clearly favored, and the end result is a dynamic equilibrium where the concentrations of monomer and dimer are very similar. We proposed that based on their variable rates of hydrolysis, the rate-limiting step of the hydrolysis cycle may differ among full-length ABC proteins. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
4. Cross-seeding between the functional amyloidogenic CRES and CRES3 family members and their regulation of Aß assembly.
- Author
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Hoa Quynh Do, Hewetson, Aveline, Borcik, Collin G., Hastert, Mary Catherine, Whelly, Sandra, Wylie, Benjamin J., Sutton, Roger Bryan, and Cornwall, Gail A.
- Subjects
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BACTERIAL proteins , *CYSTATINS , *TRANSMISSION electron microscopy , *AMYLOID - Abstract
Accumulating evidence shows that amyloids perform biological roles. We previously showed that an amyloid matrix composed of four members of the CRES subgroup of reproductive family 2 cystatins is a normal component of the mouse epididymal lumen. The cellular mechanisms that control the assembly of these and other functional amyloid structures, however, remain unclear. We speculated that cross-seeding between CRES members could be a mechanism to control the assembly of the endogenous functional amyloid. Herein we used thioflavin T assays and negative stain transmission electron microscopy to explore this possibility. We show that CRES3 rapidly formed large networks of beaded chains that possessed the characteristic cross-ß reflections of amyloid when examined by X-ray diffraction. The beaded amyloids accelerated the amyloidogenesis of CRES, a less amyloidogenic family member, in seeding assays during which beads transitioned into films and fibrils. Similarly, CRES seeds expedited CRES3 amyloidogenesis, although less efficiently than the CRES3 seeding of CRES. These studies suggest that CRES and CRES3 hetero-oligomerize and that CRES3 beaded amyloids may function as stable preassembled seeds. The CRES3 beaded amyloids also facilitated assembly of the unrelated amyloidogenic precursor Aß by providing a surface for polymerization though, intriguingly, CRES3 (and CRES) monomer/early oligomer profoundly inhibited Aß assembly. The cross-seeding between the CRES subgroup members is similar to that which occurs between bacterial curli proteins suggesting that it may be an evolutionarily conserved mechanism to control the assembly of some functional amyloids. Further, interactions between unrelated amyloidogenic precursors may also be a means to regulate functional amyloid assembly. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
5. Enzymatic cleavage of myoferlin releases a dual C2-domain module linked to ERK signalling.
- Author
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Piper, Ann-Katrin, Ross, Samuel E., Redpath, Gregory M., Lemckert, Frances A., Woolger, Natalie, Bournazos, Adam, Greer, Peter A., Sutton, Roger B., and Cooper, Sandra T.
- Subjects
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EXTRACELLULAR signal-regulated kinases , *CELLULAR signal transduction , *CHIMERIC proteins , *CELL lines , *PROTEIN expression - Abstract
Myoferlin and dysferlin are closely related members of the ferlin family of Ca 2 + -regulated vesicle fusion proteins. Dysferlin is proposed to play a role in Ca 2 + -triggered vesicle fusion during membrane repair. Myoferlin regulates endocytosis, recycling of growth factor receptors and adhesion proteins, and is linked to the metastatic potential of cancer cells. Our previous studies establish that dysferlin is cleaved by calpains during membrane injury, with the cleavage motif encoded by alternately-spliced exon 40a. Herein we describe the cleavage of myoferlin, yielding a membrane-associated dual C2 domain ‘mini-myoferlin’ . Myoferlin bears two enzymatic cleavage sites: a canonical cleavage site encoded by exon 38 within the C2 DE domain; and a second cleavage site in the linker adjacent to C2 DE , encoded by alternately-spliced exon 38a, homologous to dysferlin exon 40a. Both myoferlin cleavage sites, when introduced into dysferlin, can functionally substitute for exon 40a to confer Ca 2 + -triggered calpain cleavage in response to membrane injury. However, enzymatic cleavage of myoferlin is complex, showing both constitutive or Ca 2 + -enhanced cleavage in different cell lines, that is not solely dependent on calpains-1 or -2. The functional impact of myoferlin cleavage was explored through signalling protein phospho-protein arrays revealing specific activation of ERK1/2 by ectopic expression of cleavable myoferlin, but not an uncleavable isoform. In summary, we molecularly define two enzymatic cleavage sites within myoferlin and demonstrate ‘mini-myoferlin’ can be detected in human breast cancer tumour samples and cell lines. These data further illustrate that enzymatic cleavage of ferlins is an evolutionarily preserved mechanism to release functionally specialized mini-modules. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
6. Library Services.
- Author
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Stevens, Norman, Cohen, David, Maas, Norman L., Shepherd, Catherine, Bunge, Charles A., Cohen, Liz Dannenbaum, VanBrimmer, Barbara, Israel, Callie, Young, Richard, Sannwald, William W., Sweet, Doris Ann, Sutton, Roger, Prentice, Ann E., and Yee, Sandra G.
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NONFICTION - Abstract
Reviews several non-fiction books on library services. 'The Facts of Love in the Library: Making Sexuality Information Relevant and Accessible to Young People,' by Patty Campbell; 'Ethnic Minorities and Public Libraries: Self-help and Opportunities for Co-operation,' by Pirkko Elliott; 'The Referral Process in Libraries: A Characterization and an Exploration of Related Factors,' by George S. Hawley.
- Published
- 1988
7. Membrane fusion FerA domains enhance adeno-associated virus vector transduction.
- Author
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Zhang, Xintao, Anthony, Bui, Chai, Zheng, Lee Dobbins, Amanda, Sutton, Roger Bryan, and Li, Chengwen
- Subjects
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ADENO-associated virus , *MEMBRANE fusion , *GENETIC transduction , *BLOOD coagulation factor IX , *ADENOVIRUSES , *INTRAMUSCULAR injections , *BLOOD coagulation factors - Abstract
The recombinant adeno-associated virus (rAAV) vector has been successfully employed in clinical trials for patients with blindness and bleeding diseases as well as neuromuscular disorders. To date, it remains a major challenge to achieve higher transduction efficiency with a lower dose of rAAV vector. Our previous studies have demonstrated that serum proteins are able to directly interact with AAV virions for transduction enhancement. Herein, we explored the effect of the FerA domains, which are derived from ferlin proteins and possess membrane-fusion activity, on AAV transduction. Our results show that FerA domains from dysferlin, myoferlin, and otoferlin proteins are able to directly interact with AAV vectors and enhance AAV transduction in vitro and in mice through either intravenous or intramuscular injections. The enhanced AAV transduction induced by human/mouse FerA domains is achieved in various cell lines and in mice regardless of AAV serotypes. Mechanism studies demonstrated that the FerA domains could effectively enhance the ability of AAV vectors to bind to target cells and cross the vascular barrier. Additionally, FerA domains slow down the blood clearance of AAV. Systemic administration of AAV8/hFIX-FerA complex induced approximate 4-fold more human coagulation factor IX expression and improved hemostasis in hemophilia B mice than that of AAV8/hFIX. Collectively, we show, for the first time, that multiple FerA domains could be tethered on the AAV capsid and enhance widespread tissue distribution in an AAV serotypes-independent manner. This approach therefore holds a promise for future clinical application. • Diverse FerA domains augment AAV transduction in AAV serotypes-independent manner. • FerA domains directly interact with AAV virion. • FerA domains fuel AAV binding, trafficking, and traversing ability. • FerA domains slow down the blood clearance of AAV. • ScAAV8/hFIX-FerA injection improves hemostasis in FIX-/- hemophilia B mice. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
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