Conformational changes and disease - Serpins, prions and Alzheimer's

Current Opinion in Structural Biology

Volumn 8, Issue 6, 1998, Pages 799-809

  Carrell, Robin W ^a   Gooptu, Bibek ^a  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

PRION PROTEIN; SERINE PROTEINASE INHIBITOR;

ALZHEIMER DISEASE; AMYLOIDOSIS; BRAIN DISEASE; CONFORMATIONAL TRANSITION; DEMENTIA; ELECTRON MICROSCOPY; HUMAN; HUMAN TISSUE; PRIORITY JOURNAL; PROTEIN CONFORMATION; PROTEIN FOLDING; REVIEW;

EID: 0032425463     PISSN: 0959440X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0959-440X(98)80101-2     Document Type: Article

References (59)

1. 1. Carrell RW, Lomas DA: Conformational diseases. Lancet 1997, 350:134-138. This review categorises the diverse degenerative and other diseases that make up the new entity of the conformational diseases. Although unrelated one to another, they share a striking similarity in clinical presentations that reflect their shared molecular mechanisms of initiation and self-association, with consequent tissue deposition and damage.
2. 2. Prusiner SB: Prion diseases and the BSE crisis. Science 1997, 278:245-251. This paper reviews the range of prion diseases and their transmission, including the bovine form bovine spongiform encephalopathy and new variant Creutzfeldt-Jakob disease.
3. 3. Collinge J, Rossor M: A new variant of prion disease. Lancet 1996, 347:916-917.
4. 4. Selkoe DJ: Amyloid β-protein and the genetics of Alzheimer's disease. J Biol Chem 1996, 271:18295-18298.
5. 5. Kisilevsky R: Amyloid β threads in the fabric of Alzheimer's disease. Nat Med 1998, 4:772-773. A brief summary of the current understanding of both the pathophysiology of Alzheimer's disease and strategies for its detection and treatment.
6. 6. Phimister B: The Tao of tau. Nat Med 1998, 4:774.
7. 7. Eaton WA: Sickle cell hemoglobin polymerization. Adv Protein Chem 1990, 140:63-279.
8. 8. Whisstock J, Skinner R, Lesk AM: An atlas of serpin conformations. Trends Biochem Sci 1998, 23:63-67. A concise and clearly illustrated review of the crystallographic structures of the serpins and the conformational mobility of their reactive site peptide loops and A sheets.
9. 9. Stein PE, Carrell RW: What do dysfunctional serpins tell us about molecular mobility and disease? Nat Struct Biol 1995, 2:96-113.
10. 10. Kelly JW: Alternative conformations of amyloidogenic proteins govern their behavior. Curr Opin Struct Biol 1996, 6:11-17.
11. 11. Kelly JW: The alternative conformations of amyloidogenic proteins and their multi-step assembly pathways. Curr Opin Struct Biol 1998, 8:101-106. This, and the preceding review [10], summarise the evidence for a pathway of amyloid formation, initiated by a conformational change, to give a partly unfolded intermediate form. As mutations shift the equilibrium in favour of the amyloidogenic intermediate, the age of the onset of the disease decreases.
12. 12. Harrison PM, Bamborough P, Daggett V, Prusiner SB, Cohen FE: The prion folding problem. Curr Opin Struct Biol 1997, 7:53-59. The authors review the structural evidence for the conformational transition of prion proteins and discuss possible mechanisms of propagation.
13. 13. Glenner GG: Amyloid deposits and amyloidosis. The beta fibrilloses (part one and part two). N Engl J Med 1980, 302:1283-1292,1333-1343.
14. 14. Tan SY, Pepys MB: Amyloidosis. Histopathology 1994, 25:403-414.
15. 15. Bonar L, Cohen AS, Skinner M: Characterization of the amyloid fibril as a cross-β protein. Proc Soc Exp Biol Med 1967, 131:1373-1375.
16. 16. Sunde M, Serpell LC, Bartlam M, Fraser PE, Pepys MB, Blake CCF: Common core structure of amyloid fibrils by synchrotron X-ray diffraction. J Mol Biol 1997, 273:729-739. This paper demonstrates the remarkable similarity of X-ray fibre diffraction patterns of six different ex vivo and two synthetic amyloid fibril preparations. The authors conclude that amyloid fibrils comprise a structural superfamily with a common protofilament structure.
17. 17. Booth DR, Sunde M, Bellotti V, Robinson CV, Hutchinson WL, Fraser PE, Hawkins PN, Dobson CM, Radford SE, Blake CCF, Pepys MB: Instability, unfolding and aggregation of human lysozyme variants underlying amyloid fibrillogenesis. Nature 1997, 385:787-793. Two natural variants of lysosome, known to form amyloid, were shown to be unstable, undergoing a transformation from the mainly helical native fold to the fibrillar cross-β fold of an amyloid fibril. The loss of helicity is incomplete, but the authors suggest that aggregation involves an unfolded 'molten globule' intermediate and that this may apply to amyloid formation in general.
18. 18. Litvinovich SV, Brew SA, Aota S, Akiyama SK, Haudenschild C, Ingham KC: Formation of amyloid-like fibrils by self-association of a partially unfolded fibronectin type III module. J Mol Biol 1998, 280:245-248.
19. 19. Liu Y, Hart PJ, Schlunegger MP, Eisenberg D: The crystal structure of a 3D domain swapped dimer of RNase A at 2.1-Å resolution. Proc Natl Acad Sci USA 1998, 95:3437-3442. The swapping of a 15 residue terminal helix between two molecules of RNase A results in a dimer that binds Congo red. This domain swapping mechanism is compared to that which results in immunoglobulin light chain amyloidosis, suggesting the possibility of fibril formation being initiated by relatively minor changes, such as cleavage or release of an exchangeable domain.
20. 1-antitrypsin. Biol Chem Hoppe Seyler 1995, 375:103-109.
21. 21. Prusiner SB: Prion diseases of humans and animals. J R Coll Phys 1994, 28:1-30.
22. 22. Yankner BA: New clues to Alzheimer's disease: unraveling the roles of amyloid and tau. Nat Med 1996, 2:850-851.
23. 23. Stratikos E, Gettins PGW: Mapping the serpin-proteinase complex using single cysteine variants of α1-proteinase inhibitor Pittsburgh. J Biol Chem 1998, 273:15582-15589.
24. 1-antitrypsin deficiency. Scand J Clin Lab Invest 1963, 15:132-140.
25. 1-antitrypsin accumulation in the liver. Nature 1992, 357:605-607.
26. 1-antitrypsin deficiency, as well as for the rarer variants illustrative of the structural pathology.
27. 1-antitrypsin. Nat Struct Biol 1996, 3:676-681.
28. 28. Schreuder HA, de Boer B, Dijkema R, Mulders J, Theunisen HJM, Grootenhuis PDJ, Hol WGJ: The intact and cleared human antithrombin III complex as a model for serine proteinase inhibitors. Nat Struct Biol 1994, 1:48-54.
29. 29. Carrell RW, Stein PE, Fermi G, Wardell MR: Biological implications of a 3Å structure of dimeric antithrombin. Structure 1994, 2:257-270.
30. 30. Jin L, Abrahams JP, Skinner R, Petitou M, Pike RN, Carrell RW: The anticoagulant activation of antithrombin by heparin. Proc Natl Acad Sci USA 1997, 94:14683-14688. This paper provides the structures of a heterodimer of latent and active antithrombin, each complexed with the pentasaccharide core of heparin. It demonstrates how interaction with a small molecule results in a tightening of the tertiary structure, with induction of increased helical content and closure of the A sheet. Complete continuity of the reactive loop of the inactive molecule unequivocally confirms the latent conformation.
31. 31. Sharp AM, Stein PE, Lawrence DA, Read RJ: Active plasminogen activator inhibitor-1 structure reveals differences from latent and cleaved forms. Abstract W0030 of the Proc Am Crystall Assoc Annual Meeting, 1998, Arlington, VA.
32. 32. Mottonen J, Strand A, Symersky J, Sweet RM, Danley DE, Geoghegan KF, Gerard RD, Goldsmith EJ: Structural basis of latency in plasminogen activator inhibitor-1. Nature 1992, 355:270-273.
33. 33. Beauchamp NJ, Pike RN, Daly M, Butler L, Makris M, Dafforn TR, Zhou A, Fitton HL, Preston FE, Peake IR, Carrell RW: Antithrombins wibble and wobble (T85M/K): archetypal conformational diseases with in vivo latent-transition, thrombosis and heparin activation. Blood 1998, 92:2696-2706. Two conformationally unstable antithrombins with different mutations at the same site predispose to in vivo conversion to the latent form, with the onset, in association with incidental fever, of episodes of thrombosis. The fact that the instability results from a laxity of the closure of the A sheet is confirmed by a return to full stability upon interaction with the heparin pentasaccharide.
34. 1-antichymotrypsin in chronic bronchitis and emphysema. J Biol Chem 1998, 273:3695-3701.
35. 35. Berkenpas MB, Lawrence DA, Ginsburg D: Molecular evolution of plasminogen activator inhibitor-1 functional stability. EMBO J 1995, 14:2969-2977.
36. 1-antitrypsin that are complementary to those found in natural unstable variants result in increased stability of the closed A sheet.
37. 37. Carrell RW, Stein PE: The biostructural pathology of the serpins: critical function of sheet opening mechanism. Biol Chem Hoppe Seyler 1996, 377:1-17.
38. 38. Bruce D, Perry DJ, Borg J-Y, Carrell RW, Wardell MR: Thromboembolic disease due to thermolabile conformational changes of antithrombin Rouen VI (187 Asn→Asp). J Clin Invest 1994, 94:2265-2274.
39. 39. Griffith JS: Self-replication and scrapie. Nature 1967, 215:1043-1044.
40. 40. Prusiner SB, Scott MR, DeArmond SJ, Cohen FE: Prion protein biology. Cell 1998, 93:337-348. A comprehensive review of the genetics and structure of priori proteins, with proposed mechanisms of propagation and transmission.
41. 41. Cheseboro B: BSE and prions: uncertainties about the agent. Science 1998, 279:42-43. The case is put forward for caution in accepting the conformational propagation proposals for prion transmission. The gaps in the evidence are high-lighted, with the possibility of viral transmission not eliminated.
42. 42. Aguzzi A, Weissman C: Prion research: the next frontiers. Nature 1997, 389:795-798.
43. Sc transformation. The findings provide an explanation for the protective effect of basic residues in some isoforms of prion proteins in sheep and humans.
44. 44. Zhou A, Jin L, Huntington JA, Carrell RW: Serine protease inhibitors and thrombosis (Abstract). Br J Haematol 1998, 102:157.
45. 45. Laurent M: Autocatalytic processes in co-operative mechanisms of prion diseases. FEBS Lett 1997, 407:1-6.
46. 46. Geula C, Wu C-K, Saroff D, Lorenzo A, Yuan M, Yankner BA: Ageing renders the brain vulnerable to amyloid β-protein neurotoxicity. Nat Med 1998, 4:827-831. The microinjection of fibrillar Aβ peptides into the cerebral cortex of aged, but not young, primates results in the full changes observed in Alzheimer's disease, including tau phosphorylation and microglial proliferation.
47. 47. Beyreuther K, Masters CL: Alzheimer's disease. Tangle disentanglement. Nature 1996, 383:476-477.
48. 48. Hutton M, Lendon CL, Rizzu P, Baker M, Froelich S, Houlden H, Pickering-Brown S, Chakraverty S, Isaacs A, Grover A et al.: Association of missense and 5′-splice-site mutations in Tau with the inherited dementia FTDP-17. Nature 1998, 393:702-705. This is the most comprehensive, but not the first, of several papers (see [6]) showing missense tau mutations in individuals with a type of frontotemporal dementia. The lesions show neurofibrillary tangles of tau protein and frontotemporal lobe atrophy of the brain.
49. 1-antitrypsin, reversal of polymer formation. See, also [50•].
50. 50. Xue Y, Björquist P, Inghardt T, Linschoten M, Musil D, Sjölin L, Deinum J: Interfering with the inhibitory mechanism of serpins: crystal structure of a complex formed between cleaved plasminogen activator inhibitor type 1 and a reactive-centre loop peptide. Structure 1998, 6:627-636. The annealing of homologue peptides prevents reactive loop insertion and, hence, transition to the latent conformation. See, also, the annotation to [49•].
51. 51. Soto C, Sigurdsson EM, Morelli L, Asok Kumar R, Castano EM, Frangione B: β-sheet breaker peptides inhibit fibrillogenesis in a rat brain model of amyloidosis: implications for Alzheimer's therapy. Nat Med 1998, 4:822-826. A proline-substituted pentapeptide, homologous to the amyloid β peptide of Alzheimer's disease, inhibits amyloid fibrillogenesis in vitro and blocks the formation of amyloid fibrils in a rat brain model.
52. 1-antitrypsin reveals a hydrophobic pocket, located between the A sheet and helices D and E, that is obscured upon the conformational transition of the molecule.
53. 53. Björquist P, Ehnebom J, Inghardt L, Lindberg M, Linschoten M, Strömqvist M, Deinum J: Identification of the binding site for a low-molecular-weight inhibitor of plasminogen activator inhibitor type 1 by site-directed mutagenesis. Biochemistry 1998, 37:1227-1234. There are now several fungal and other small heterocyclic compounds that are known to inactivate the function of the inhibitor of fibrinolysis, PAI-1. This paper describes recombinant-based studies implicating a site between the A sheet and helices D and E. This approximates to the pocket independently identified using crystallography in [52•].
54. 54. Snow AD, Kisilevsky R: Temporal relationship between glycosaminoglycan accumulation and amyloid deposition during experimental amyloidosis. A histochemical study. Lab Invest 1985, 53:37-44.
55. 55. Castillo GM, Ngo C, Cummings J, Wight TN, Snow AD: Perlecan binds to the β-amyloid proteins (Aβ) of Alzheimer's disease, accelerates Aβ fibril formation, and maintains Aβ fibril stability. J Neurochem 1997, 69:2452-2465. This study investigates a specific proteoglycan that accumulates in the fibrillar β-amyloid deposits of Alzheimer's disease. It is shown to not only bind to the critical Aβ isoforms, but also to accelerate fibril formation and provide subsequent fibril stabilisation.
56. 56. Kisilevsky R, Lemieux LJ, Fraser PE, Kong X, Hultin PG, Szarek WA: Arresting amyloidosis in vivo using small molecule anionic sulphonates or sulphates: implications for Alzheimer's disease. Nat Med 1995, 1:143-148.
57. 57. Carrell RW, Lehmann H, Hutchison HE: Haemoglobin Köln (β98 valine→methionine): unstable protein causing inclusion-body anaemia. Nature 1966, 210:915-916.
58. 58. Abrahamson M, Grubb A: Increased body temperature accelerates aggregation of the Leu-68→Gln mutant cystatin C, the amyloid-forming protein in hereditary cystatin C amyloid angiopathy. Proc Natl Acad Sci USA 1994, 91:1416-1420.
59. 59. Goedert M, Jakes R, Spillantini MG, Hasegawa M, Smith MJ, Crowther RA: Assembly of microtubule-associated protein tau into Alzheimer-like filaments induced by sulphated glycosaminoglycans. Nature 1996, 383:550-553.