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Genomes and Genes | Robin W CarrellSummaryAffiliation: University of Cambridge Country: UK Publications
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Publications
How serpins are shaping upR W Carrell
Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Hills Road, Cambridge CB2 2XY, UK
Science 285:1861. 1999- What can Drosophila tell us about serpins, thrombosis and dementia?Robin Carrell
University of Cambridge, Cambridge Institute of Medical Research, Cambridge, UK
Bioessays 26:1-5. 2004..The findings provide clues as to the unusual severity and variable onset of such conformational diseases and demonstrate the potential of Drosophila as a model for their future study... - Biomedicine. Prion dormancy and diseaseRobin W Carrell
Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 2XY, UK
Science 306:1692-3. 2004 - Cell toxicity and conformational diseaseRobin W Carrell
Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK CB2 2XY
Trends Cell Biol 15:574-80. 2005..The challenge now is to determine the detailed mechanisms of this cytotoxicity... - What we owe to alpha(1)-antitrypsin and to Carl-Bertil LaurellRobin W Carrell
Cambridge Institute for Medical Research, University of Cambridge, CB2 2XY, Cambridge, UK
COPD 1:71-84. 2004..Time after time, scientific controversies and deadlocks have been solved by landmark clinical cases, which have revealed unexpected findings and insights, within and beyond the fields of study... - Alpha1-antitrypsin deficiency--a model for conformational diseasesRobin W Carrell
Department of Hematology, University of Cambridge, Cambridge Institute for Medical Research, Cambridge, United Kingdom
N Engl J Med 346:45-53. 2002 
Serpins show structural basis for oligomer toxicity and amyloid ubiquityRobin W Carrell
Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK
FEBS Lett 582:2537-41. 2008..We illustrate how the preferential self-association that gives this protection has been selectively favoured...- The conformational basis of thrombosisR W Carrell
Department of Haematology, University of Cambridge, Wellcome Trust Centre for Molecular Mechanisms in Disease, UK
Thromb Haemost 86:14-22. 2001..The precise structural pathway, now known with antithrombin, provides a model of the changes occurring in other conformational diseases, including Alzheimer's and the prion dementias... - Structure of a serpin-protease complex shows inhibition by deformationJ A Huntington
Department of Haematology, University of Cambridge, Wellcome Trust Centre for Molecular Mechanisms in Disease, Cambridge Institute for Medical Research, UK
Nature 407:923-6. 2000..It is this ability of the conformational mechanism to crush as well as inhibit proteases that provides the serpins with their selective advantage... - Crystal structure of protein Z-dependent inhibitor complex shows how protein Z functions as a cofactor in the membrane inhibition of factor XZhenquan Wei
Department of Haematology, University of Cambridge, Cambridge Institute for Medical Research, Cambridge, United Kingdom
Blood 114:3662-7. 2009.... - Heparin-induced substrate behavior of antithrombin Cambridge IIAlec Mushunje
Department of Haematology, Cambridge Institute for Medical Research, Wellcome Trust MRC Building, Hills Road, Cambridge CB2 2XY, United Kingdom
Blood 102:4028-34. 2003..The high occurrence of this mutation and its possible propagation from a few founders suggests an evolutionary advantage, perhaps in decreasing postpartum bleeding... - 6-mer peptide selectively anneals to a pathogenic serpin conformation and blocks polymerization. Implications for the prevention of Z alpha(1)-antitrypsin-related cirrhosisRavi Mahadeva
Respiratory Medicine Unit, Department of Medicine, University of Cambridge, Cambridge CB2 2XY, United Kingdom
J Biol Chem 277:6771-4. 2002..Furthermore they demonstrate how a conformational disease process can be selectively inhibited with a small peptide... - Dimers initiate and propagate serine protease inhibitor polymerisationAiwu Zhou
Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Hills Road, Cambridge CB2 2XY, UK
J Mol Biol 375:36-42. 2008.... - Serpin polymerization is prevented by a hydrogen bond network that is centered on his-334 and stabilized by glycerolAiwu Zhou
Department of Haematology, University of Cambridge, Cambridge Institute of Medical Research, Hills Road, Cambridge CB2 2XY, United Kingdom
J Biol Chem 278:15116-22. 2003..This is highlighted here by the crystallographic demonstration that glycerol, which at high concentrations blocks polymerization, can replace the P8 threonine and re-form the disrupted H-bond network with His-334... - Structural mechanism for the carriage and release of thyroxine in the bloodAiwu Zhou
Departments of Haematology and Medicine, Cambridge Institute for Medical Research, University of Cambridge, Hills Road, Cambridge CB2 2XY, United Kingdom
Proc Natl Acad Sci U S A 103:13321-6. 2006..The complexity and ready triggering of this conformational mechanism strongly indicates that TBG has evolved to allow a modulated and targeted delivery of thyroxine to the tissues... - Antithrombin 'DREUX' (Lys 114Glu): a variant with complete loss of heparin affinityAlec Mushunje
Department of Haematology, University of Cambridge, Institute of Medical Research, UK
Thromb Haemost 88:436-43. 2002..However, no change in fluorescence was detected for the variant when titrated with heparin or the heparin pentasaccharide, nor was there detectable activation towards factor Xa, indicating a complete loss of heparin binding... 
The S-to-R transition of corticosteroid-binding globulin and the mechanism of hormone releaseAiwu Zhou
Department of Haematology and Medicine, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK
J Mol Biol 380:244-51. 2008..The change in the hormone binding affinity results from a change in the flexibility or plasticity of the connecting loop, which modulates the configuration of the binding site...- A redox switch in angiotensinogen modulates angiotensin releaseAiwu Zhou
Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK
Nature 468:108-11. 2010.... - Serpinopathies and the conformational dementiasDavid A Lomas
Department of Medicine, University of Cambridge, Cambridge Institute for Medical Research, Wellcome Trust MRC Building, Hills Road, Cambridge CB2 2XY, UK
Nat Rev Genet 3:759-68. 2002.... - How small peptides block and reverse serpin polymerisationAiwu Zhou
Departments of Haematology and Medicine, University of Cambridge, Cambridge Institute for Medical Research, Hills Road, Cambridge CB2 2XY, UK
J Mol Biol 342:931-41. 2004..This is demonstrated here with a tetrapeptide that preferentially blocks the polymerisation of a pathologically unstable serpin commonly present in people of European descent... - Crystal structures of native and thrombin-complexed heparin cofactor II reveal a multistep allosteric mechanismTrevor P Baglin
Department of Haematology, Cambridge Institute for Medical Research, Wellcome Trust MRC Building, Hills Road, Cambridge CB2 2XY, United Kingdom
Proc Natl Acad Sci U S A 99:11079-84. 2002..Together, these structures reveal a multistep allosteric mechanism that relies on sequential contraction and expansion of the central beta-sheet of HCII... - How vitronectin binds PAI-1 to modulate fibrinolysis and cell migrationAiwu Zhou
Department of Haematology, University of Cambridge, Cambridge Institute for Medical Research, Wellcome Trust MRC Building, Hills Road, Cambridge CB2 2XY, UK
Nat Struct Biol 10:541-4. 2003..Structural understanding of the essential biological roles of the interaction between PAI-1 and vitronectin opens the prospect of specifically designed blocking agents for the prevention of thrombosis and treatment of cancer... - Murine serpin 2A is a redox-sensitive intracellular proteinEmma C Morris
Department of Haematology, University College Hospital, Grafton Way, London WC1E 6AU, UK
Biochem J 371:165-73. 2003..Furthermore, the results presented suggest a model whereby the serpin interactions could be modulated by redox conditions or conformational change induced by cleavage of the reactive-site loop... - Helix D elongation and allosteric activation of antithrombinKlara J Belzar
Department of Haematology, University of Cambridge, Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Hills Rd, Cambridge CB2 2XY, United Kingdom
J Biol Chem 277:8551-8. 2002..We conclude that helix D elongation is critical for the full conversion of antithrombin to its high affinity, activated state, and we propose a mechanism to explain how helix D elongation is coupled to allosteric activation... - Structure of beta-antithrombin and the effect of glycosylation on antithrombin's heparin affinity and activityAirlie J McCoy
Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust/MRC Building, Hills Road, Cambridge CB2 2XY, UK
J Mol Biol 326:823-33. 2003.... - Association between conformational mutations in neuroserpin and onset and severity of dementiaRichard L Davis
Department of Pathology, Upstate Medical University, Syracuse, NY, USA
Lancet 359:2242-7. 2002..To clarify this issue, we investigated five families with typical neuroserpin inclusion bodies but with various neurological manifestations... - Introduction of a mutation in the shutter region of antithrombin (Phe77 --> Leu) increases affinity for heparin and decreases thermal stabilityNoelene S Quinsey
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia
Biochemistry 42:10169-73. 2003..This paper also demonstrates that there are major differences between the shutter regions of antithrombin and alpha(1)-antitrypsin since a stabilizing mutation in antitrypsin has the converse effect in antithrombin... - Homozygous deficiency of heparin cofactor II: relevance of P17 glutamate residue in serpins, relationship with conformational diseases, and role in thrombosisJavier Corral
University of Murcia, Centro Regional de Hemodonación de Murcia, Murcia, Spain
Circulation 110:1303-7. 2004..Recent data obtained in mice lacking HCII suggest that this serpin might inhibit thrombosis in the arterial circulation. However, the clinical relevance and molecular mechanisms associated with deficiency of HCII in humans are unclear... - Thrombosis as a conformational diseaseJavier Corral
Universidad de Murcia Centro Regional de Hemodonación, Spain
Haematologica 90:238-46. 2005..The search for other causes is important, as the conformational perturbation of normal antithrombin is likely to be a contributory cause to the sporadic and apparently idiopathic occurrence of venous thrombosis...