Deciphering a molecular mechanism of neonatal diabetes mellitus by the chemical synthesis of a protein diastereomer, [D-AlaB8]human proinsulin

Journal of Biological Chemistry

Volumn 289, Issue 34, 2014, Pages 23683-23692

  Avital Shmilovici, Michal ^a   Whittaker, Jonathan ^b   Weiss, Michael A ^b,c   Kent, Stephen B H ^a  

^a UNIVERSITY OF CHICAGO   (United States)

^b CASE WESTERN RESERVE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c Case Western Reserve University   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACIDS; MOLECULES; PHYSIOLOGY; PROTEINS; SYNTHESIS (CHEMICAL);

CHEMICAL LIGATION; DIABETES MELLITUS; GAIN-OF FUNCTION; INSULIN RECEPTORS; MOLECULAR MECHANISM; PHYSIOLOGICAL CONDITION; PROTEIN DISULFIDE ISOMERASES; PROTEIN MOLECULES;

INSULIN;

ALANINE; INSULIN RECEPTOR; PROINSULIN; PROTEIN DISULFIDE ISOMERASE;

ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; DIABETES MELLITUS; DIASTEREOISOMER; MOLECULAR DYNAMICS; PRIORITY JOURNAL; PROTEIN DETERMINATION; PROTEIN FOLDING; PROTEIN SYNTHESIS; RECEPTOR BINDING; STEREOCHEMISTRY; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS; WILD TYPE; CHEMISTRY; ELECTROSPRAY MASS SPECTROMETRY; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; METABOLISM; NEWBORN; NEWBORN DISEASE; REVERSED PHASE LIQUID CHROMATOGRAPHY; STEREOISOMERISM; SYNTHESIS;

ALANINE; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; CHROMATOGRAPHY, REVERSE-PHASE; DIABETES MELLITUS; HUMANS; INFANT, NEWBORN; INFANT, NEWBORN, DISEASES; PROINSULIN; SPECTROMETRY, MASS, ELECTROSPRAY IONIZATION; STEREOISOMERISM;

EID: 84906546263     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M114.572040     Document Type: Article

References (58)

1. Shield, J. P., Gardner, R. J., Wadsworth, E. J., Whiteford, M. L., James, R. S., Robinson, D. O., Baum, J. D., and Temple, I. K. (1997) Aetiopathology andgenetic basis of neonatal diabetes. Arch. Dis. Child. Fetal Neonatal Ed. 76, F39-F42
2. Støy, J., Edghill, E. L., Flanagan, S. E., Ye, H., Paz, V. P., Pluzhnikov, A., Below, J. E., Hayes, M. G., Cox, N. J., Lipkind, G. M., Lipton, R. B., Greeley, S. A., Patch, A. M., Ellard, S., Steiner, D. F., Hattersley, A. T., Philipson, L. H., Bell, G. I., and Neonatal Diabetes International Collaborative Group. (2007) Insulin gene mutations as a cause of permanent neonatal diabetes. Proc. Natl. Acad. Sci. U.S.A. 104, 15040-15044
3. Colombo, C., Porzio, O., Liu, M., Massa, O., Vasta, M., Salardi, S., Beccaria, L., Monciotti, C., Toni, S., Pedersen, O., Hansen, T., Federici, L., Pesavento, R., Cadario, F., Federici, G., Ghirri, P., Arvan, P., Iafusco, D., Barbetti, F., and Early Onset Diabetes Study Group of the Italian Society of Pediatric Endocrinology and Diabetes (SIEDP) (2008) Seven mutations in the human insulin gene linked to permanent neonatal/infancy-onset diabetes mellitus. J. Clin. Investig. 118, 2148-2156
4. Edghill, E. L., Flanagan, S. E., Patch, A. M., Boustred, C., Parrish, A., Shields, B., Shepherd, M. H., Hussain, K., Kapoor, R. R., Malecki, M., MacDonald, M. J., Støy, J., Steiner, D. F., Philipson, L. H., Bell, G. I., Neonatal Diabetes International Collaborative Group, Hattersley, A. T., and Ellard, S. (2008) Mutations in the INS gene are a common cause of neonatal diabetes but a rare cause of diabetes diagnosed in childhood or adulthood. Diabetes 57, 1034-1042
5. Molven, A., Ringdal, M., Nordbø, A. M., Raeder, H., Støy, J., Lipkind, G. M., Steiner, D. F., Philipson, L. H., Bergmann, I., Aarskog, D., Undlien, D. E., Joner, G., Søvik, O., Norwegian Childhood Diabetes Study Group, Bell, G. I., and Njølstad, P. R. (2008) Mutations in the insulin gene can cause MODY and autoantibody-negative type 1 diabetes. Diabetes 57, 1131-1135
6. Weiss, M. A. (2013) Diabetes mellitus due to the toxic misfolding of proinsulin variants. FEBS Lett. 587, 1942-1950
7. Nakagawa, S. H., Zhao, M., Hua, Q. X., Hu, S. Q., Wan, Z. L., Jia, W., and Weiss, M. A. (2005) Chiral mutagenesis of insulin: foldability and function are inversely regulated by a stereospecific switch in the B chain. Biochemistry 44, 4984-4999
8. Hua, Q. X., Nakagawa, S., Hu, S. Q., Jia, W., Wang, S., and Weiss, M. A. (2006) Toward the active conformation of insulin: stereospecific modulation of a structural switch in the B chain. J. Biol. Chem. 281, 24900-24909
9. Hua, Q. X., Shoelson, S. E., Kochoyan, M., and Weiss, M. A. (1991) Receptor binding redefined by a structural switch in a mutant human insulin. Nature 354, 238-241
10. Derewenda, U., Derewenda, Z., Dodson, E. J., Dodson, G. G., Reynolds, C. D., Smith, G. D., Sparks, C., and Swenson, D. (1989) Phenol stabilizes more helix in a new symmetrical zinc insulin hexamer. Nature 338, 594-596
11. Hua, Q. X., Hu, S. Q., Frank, B. H., Jia, W., Chu, Y. C., Wang, S. H., Burke, G. T., Katsoyannis, P. G., and Weiss, M. A. (1996) Mapping the functional surface of insulin by design: structure and function of a novel A-chain analogue. J. Mol. Biol. 264, 390-403
12. Olsen, H. B., Ludvigsen, S., and Kaarsholm, N. C. (1996) Solution structure of an engineered insulin monomer at neutral pH. Biochemistry 35, 8836-8845
13. Baker, E. N., Blundell, T. L., Cutfield, J. F., Cutfield, S. M., Dodson, E. J., Dodson, G. G., Crowfoot Hodgkin, D. M., Hubbard, R. E., Isaacs, N. W., Reynolds, C. D., Sakabe, K., Sakabe, N., and Vijayan, N. M. (1988) The structure of 2Zn pig insulin crystals at 1.5-Å resolution. Philos. Trans. R. Soc. Lond. B Biol. Sci. 319, 369-456
14. Nakagawa, S. H., Hua, Q. X., Hu, S. Q., Jia, W., Wang, S., Katsoyannis, P. G., and Weiss, M. A. (2006) Chiral mutagenesis of insulin: contribution of the B20-B23 β-turn to activity and stability. J. Biol. Chem. 281, 22386-22396
15. Noiva, R. (1999) Protein disulfide isomerase: the multifunctional redox chaperone of the endoplasmic reticulum. Semin. Cell Dev. Biol. 10, 481-493
16. Wang, C. C. (1998) Isomerase and chaperone activities of protein disulfide isomerase are both required for its function as a foldase. Biochemistry 63, 407-412
17. Frand, A. R., Cuozzo, J. W., and Kaiser, C. A. (2000) Pathways for protein disulphide bond formation. Trends Cell Biol. 10, 203-210
18. Tu, B. P., Ho-Schleyer, S. C., Travers, K. J., and Weissman, J. S. (2000) Biochemical basis of oxidative protein folding in the endoplasmic reticulum. Science 290, 1571-1574
19. Winter, J., Klappa, P., Freedman, R. B., Lilie, H., and Rudolph, R. (2002) Catalytic activity and chaperone function of human protein-disulfide isomerase are required for the efficient refolding of proinsulin. J. Biol. Chem. 277, 310-317
20. Freychet, P. (1974) The interactions of proinsulin with insulin receptors on the plasma membrane of the liver. J. Clin. Investig. 54, 1020-1031
21. Mitchell, A. R., Kent, S. B. H., Engelhard, M., and Merrifield, R. B. (1978) A new synthetic route to tert-butyloxycarbonylaminoacyl-4-(oxymethyl)- phenylacetamidomethyl-resin, an improved support for solid-phase peptide synthesis. J. Org. Chem. 43, 2845-2852
22. Schnölzer, M., Alewood, P., Jones, A., Alewood, D., and Kent, S. B. H. (2007) In situ neutralization in Boc-chemistry solid phase peptide synthesis. Int. J. Pept. Res. Ther. 13, 31-44
23. Hackeng, T. M., Griffin, J. H., and Dawson, P. E. (1999) Protein synthesis by native chemical ligation: expanded scope by using straightforward methodology. Proc. Natl. Acad. Sci. U.S.A. 96, 10068-10073
24. Johnson, E. C., and Kent, S. B. (2006) Insights into the mechanism and catalysis of the native chemical ligation reaction. J. Am. Chem. Soc. 128, 6640-6646
25. Villain, M., Vizzavona, J., and Rose, K. (2001) Covalent capture: a new tool for the purification of synthetic and recombinant polypeptides. Chem. Biol. 8, 673-679
26. Luisier, S., Avital-Shmilovici, M., Weiss, M. A., and Kent, S. B. (2010) Total chemical synthesis of human proinsulin. Chem. Commun. (Camb). 46, 8177-8179
27. Mackin, R. B., and Choquette, M. H. (2003) Expression, purification, and PC1-mediated processing of (H10D, P28K, and K29P)-human proinsulin. Protein Expr. Purif. 27, 210-219
28. Whittaker, J., and Whittaker, L. (2005) Characterization of the functional insulin binding epitopes of the full-length insulin receptor. J. Biol. Chem. 280, 20932-20936
29. Sohma, Y., Hua, Q. X., Liu, M., Phillips, N. B., Hu, S. Q., Whittaker, J., Whittaker, L. J., Ng, A., Roberts, C. T., Jr., Arvan, P., Kent, S. B., and Weiss, M. A. (2010) Contribution of residue B5 to the folding and function of insulin and IGF-I: constraints and fine-tuning in the evolution of a protein family. J. Biol. Chem. 285, 5040-5055
30. Bang, D., and Kent, S. B. (2004) A one-pot total synthesis of crambin. Angew. Chem. Int. Ed. Engl. 43, 2534-2538
31. Dawson, P. E., Muir, T. W., Clark-Lewis, I., and Kent, S. B. (1994) Synthesis of proteins by native chemical ligation. Science 266, 776-779
32. Kent, S. B. (2009) Total chemical synthesis of proteins. Chem. Soc. Rev. 38, 338-351
33. Winter, J., Lilie, H., and Rudolph, R. (2002) Renaturation of human proinsulin: a study on refolding and conversion to insulin. Anal. Biochem. 310, 148-155
34. Anfinsen, C. B. (1973) Principles the govern the folding of protein chains. Science 181, 223-230
35. Dill, K. A., and Chan, H. S. (1997) From Levinthal to pathways to funnels. Nat. Struct. Biol. 4, 10-19
36. Karplus, M. (1997) The Levinthal paradox: yesterday and today. Fold. Des. 2, S69-S75
37. Sali, A., Shakhnovich, E., and Karplus, M. (1994) How does a protein fold?. Nature 369, 248-251
38. Zeldovich, K. B., and Shakhnovich, E. I. (2008) Understanding protein evolution: from protein physics to Darwinian selection. Annu. Rev. Phys. Chem. 59, 105-127
39. Alm, E., and Baker, D. (1999) Prediction of protein-folding mechanisms from free-energy landscapes derived from native structures. Proc. Natl. Acad. Sci. U.S.A. 96, 11305-11310
40. Creighton, T. E. (1992) What the papers say: protein folding pathways determined using disulphide bonds. Bioessays 14, 195-199
41. Schaeffer, R. D., Fersht, A., and Daggett, V. (2008) Combining experiment and simulation in protein folding: closing the gap for small model systems. Curr. Opin. Struct. Biol. 18, 4-9
42. Chiti, F., and Dobson, C. M. (2006) Protein misfolding, functional amyloid, and human disease. Annu. Rev. Biochem. 75, 333-366
43. Dobson, C. M. (2003) Protein folding and misfolding. Nature 426, 884-890
44. Connelly, S., Choi, S., Johnson, S. M., Kelly, J. W., and Wilson, I. A. (2010) Structure-based design of kinetic stabilizers that ameliorate the transthyretin amyloidoses. Curr. Opin. Struct. Biol. 20, 54-62
45. Ron, D. (2002) Proteotoxicity in the endoplasmic reticulum: lessons from the Akita diabetic mouse. J. Clin. Invest. 109, 443-445
46. Zhao, L., and Ackerman, S. L. (2006) Endoplasmic reticulum stress in health and disease. Curr. Opin. Cell Biol. 18, 444-452
47. Fonseca, S. G., Gromada, J., and Urano, F. (2011) Endoplasmic reticulum stress and pancreatic β-cell death. Trends Endocrinol. Metab. 22, 266-274
48. Liu, M., Wan, Z. L., Chu, Y. C., Aladdin, H., Klaproth, B., Choquette, M., Hua, Q. X., Mackin, R. B., Rao, J. S., De Meyts, P., Katsoyannis, P. G., Arvan, P., and Weiss, M. A. (2009) Crystal structure of a " nonfoldable" insulin: impaired folding efficiency despite native activity. J. Biol. Chem. 284, 35259-35272
49. Katsoyannis, P. G. (1966) Synthesis of insulin. Science 154, 1509-1514
50. Sohma, Y., and Kent, S. B. (2009) Biomimetic synthesis of lispro insulin via a chemically synthesized "mini-proinsulin" prepared by oxime-forming ligation. J. Am. Chem. Soc. 131, 16313-16318
51. Bentley, G., Dodson, E., Dodson, G., Hodgkin, D., and Mercola, D. (1976) Structure of insulin in 4-zinc insulin. Nature 261, 166-168
52. De Meyts, P., and Whittaker, J. (2002) Structural biology of insulin and IGF1 receptors: implications for drug design. Nat. Rev. Drug Discov. 1, 769-783
53. Liu, M., Hodish, I., Haataja, L., Lara-Lemus, R., Rajpal, G., Wright, J., and Arvan, P. (2010) Proinsulin misfolding and diabetes: mutant INS geneinduced diabetes of youth. Trends Endocrinol. Metab. 21, 652-659
54. DCCT. (1993) The Effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N. Engl. J. Med. 329, 977-986
55. Nathan, D. M., Cleary, P. A., Backlund, J. Y., Genuth, S. M., Lachin, J. M., Orchard, T. J., Raskin, P., and Zinman, B. (2005) Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N. Engl. J. Med. 353, 2643-2653
56. Fink, A. L. (2005) Natively unfolded proteins. Curr. Opin. Struct. Biol. 15, 35-41
57. Avital-Shmilovici, M., Mandal, K., Gates, Z. P., Phillips, N. B., Weiss, M. A., and Kent, S. B. (2013) Fully convergent chemical synthesis of ester insulin: determination of the high resolution x-ray structure by racemic protein crystallography. J. Am. Chem. Soc. 135, 3173-3185
58. Menting, J. G., Whittaker, J., Margetts, M. B., Whittaker, L. J., Kong, G. K., Smith, B. J., Watson, C. J., Záaovø, L., Kletvíovø, E., Jiráček, J., Chan, S. J., Steiner, D. F., Dodson, G. G., Brzozowski, A. M., Weiss, M. A., Ward, C. W., and Lawrence, M. C. (2013) How insulin engages its primary binding site on the insulin receptor. Nature 493, 241-245