Robin W Carrell

Summary

Affiliation: University of Cambridge
Country: UK

Publications

  1. ncbi request reprint How serpins are shaping up
    R W Carrell
    Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Hills Road, Cambridge CB2 2XY, UK
    Science 285:1861. 1999
  2. ncbi request reprint Cell toxicity and conformational disease
    Robin W Carrell
    Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK CB2 2XY
    Trends Cell Biol 15:574-80. 2005
  3. ncbi request reprint 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
  4. ncbi request reprint What we owe to alpha(1)-antitrypsin and to Carl-Bertil Laurell
    Robin W Carrell
    Cambridge Institute for Medical Research, University of Cambridge, CB2 2XY, Cambridge, UK
    COPD 1:71-84. 2004
  5. ncbi request reprint Biomedicine. Prion dormancy and disease
    Robin W Carrell
    Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 2XY, UK
    Science 306:1692-3. 2004
  6. pmc Serpins show structural basis for oligomer toxicity and amyloid ubiquity
    Robin W Carrell
    Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK
    FEBS Lett 582:2537-41. 2008
  7. ncbi request reprint Alpha1-antitrypsin deficiency--a model for conformational diseases
    Robin W Carrell
    Department of Hematology, University of Cambridge, Cambridge Institute for Medical Research, Cambridge, United Kingdom
    N Engl J Med 346:45-53. 2002
  8. ncbi request reprint Structure of a serpin-protease complex shows inhibition by deformation
    J 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
  9. ncbi request reprint The conformational basis of thrombosis
    R W Carrell
    Department of Haematology, University of Cambridge, Wellcome Trust Centre for Molecular Mechanisms in Disease, UK
    Thromb Haemost 86:14-22. 2001
  10. pmc Crystal structure of protein Z-dependent inhibitor complex shows how protein Z functions as a cofactor in the membrane inhibition of factor X
    Zhenquan Wei
    Department of Haematology, University of Cambridge, Cambridge Institute for Medical Research, Cambridge, United Kingdom
    Blood 114:3662-7. 2009

Collaborators

Detail Information

Publications30

  1. ncbi request reprint How serpins are shaping up
    R W Carrell
    Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Hills Road, Cambridge CB2 2XY, UK
    Science 285:1861. 1999
  2. ncbi request reprint Cell toxicity and conformational disease
    Robin 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...
  3. ncbi request reprint 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...
  4. ncbi request reprint What we owe to alpha(1)-antitrypsin and to Carl-Bertil Laurell
    Robin 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...
  5. ncbi request reprint Biomedicine. Prion dormancy and disease
    Robin W Carrell
    Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 2XY, UK
    Science 306:1692-3. 2004
  6. pmc Serpins show structural basis for oligomer toxicity and amyloid ubiquity
    Robin 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...
  7. ncbi request reprint Alpha1-antitrypsin deficiency--a model for conformational diseases
    Robin W Carrell
    Department of Hematology, University of Cambridge, Cambridge Institute for Medical Research, Cambridge, United Kingdom
    N Engl J Med 346:45-53. 2002
  8. ncbi request reprint Structure of a serpin-protease complex shows inhibition by deformation
    J 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...
  9. ncbi request reprint The conformational basis of thrombosis
    R 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...
  10. pmc Crystal structure of protein Z-dependent inhibitor complex shows how protein Z functions as a cofactor in the membrane inhibition of factor X
    Zhenquan Wei
    Department of Haematology, University of Cambridge, Cambridge Institute for Medical Research, Cambridge, United Kingdom
    Blood 114:3662-7. 2009
    ....
  11. ncbi request reprint Heparin-induced substrate behavior of antithrombin Cambridge II
    Alec 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...
  12. ncbi request reprint 6-mer peptide selectively anneals to a pathogenic serpin conformation and blocks polymerization. Implications for the prevention of Z alpha(1)-antitrypsin-related cirrhosis
    Ravi 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...
  13. ncbi request reprint Dimers initiate and propagate serine protease inhibitor polymerisation
    Aiwu 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
    ....
  14. ncbi request reprint Serpin polymerization is prevented by a hydrogen bond network that is centered on his-334 and stabilized by glycerol
    Aiwu 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...
  15. ncbi request reprint Antithrombin 'DREUX' (Lys 114Glu): a variant with complete loss of heparin affinity
    Alec 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...
  16. pmc Structural mechanism for the carriage and release of thyroxine in the blood
    Aiwu 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...
  17. pmc A redox switch in angiotensinogen modulates angiotensin release
    Aiwu Zhou
    Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK
    Nature 468:108-11. 2010
    ....
  18. ncbi request reprint Serpinopathies and the conformational dementias
    David 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
    ....
  19. doi request reprint The S-to-R transition of corticosteroid-binding globulin and the mechanism of hormone release
    Aiwu 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...
  20. ncbi request reprint How small peptides block and reverse serpin polymerisation
    Aiwu 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...
  21. pmc How changes in affinity of corticosteroid-binding globulin modulate free cortisol concentration
    Wee Lee Chan
    Department of Hematology, University of Cambridge, Cambridge Institute for Medical Research, Cambridge CB2 0XY, United Kingdom
    J Clin Endocrinol Metab 98:3315-22. 2013
    ..We show how CBG binding affinity can vary to give changes in free cortisol concentration in a physiologically relevant range...
  22. pmc Murine serpin 2A is a redox-sensitive intracellular protein
    Emma 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...
  23. ncbi request reprint How vitronectin binds PAI-1 to modulate fibrinolysis and cell migration
    Aiwu 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...
  24. pmc Crystal structures of native and thrombin-complexed heparin cofactor II reveal a multistep allosteric mechanism
    Trevor 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...
  25. ncbi request reprint Helix D elongation and allosteric activation of antithrombin
    Klara 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...
  26. ncbi request reprint Structure of beta-antithrombin and the effect of glycosylation on antithrombin's heparin affinity and activity
    Airlie 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
    ....
  27. ncbi request reprint Association between conformational mutations in neuroserpin and onset and severity of dementia
    Richard 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...
  28. ncbi request reprint Thrombosis as a conformational disease
    Javier Corral
    Universidad de Murcia Centro Regional de HemodonaciĆ³n, 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...
  29. ncbi request reprint Homozygous deficiency of heparin cofactor II: relevance of P17 glutamate residue in serpins, relationship with conformational diseases, and role in thrombosis
    Javier Corral
    University of Murcia, Centro Regional de HemodonaciĆ³n 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...
  30. ncbi request reprint Introduction of a mutation in the shutter region of antithrombin (Phe77 --> Leu) increases affinity for heparin and decreases thermal stability
    Noelene 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...