Folding mechanism of the metastable serpin α 1-antitrypsin

Proceedings of the National Academy of Sciences of the United States of America

Volumn 109, Issue 12, 2012, Pages 4467-4472

  Tsutsui, Yuko ^a,c   Dela Cruz, Richard ^b   Wintrode, Patrick L ^a,d  

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

^b UNIVERSITY OF UTAH SCHOOL OF MEDICINE   (United States)

^c NATIONAL CANCER INSTITUTE   (United States)

^d UNIVERSITY OF MARYLAND SCHOOL OF PHARMACY   (United States)

Author keywords

Hydrogen exchange; Misfolding disease; Protein folding

Indexed keywords

ALPHA 1 ANTITRYPSIN;

ARTICLE; BETA SHEET; CARBOXY TERMINAL SEQUENCE; DEUTERIUM HYDROGEN EXCHANGE; HUMAN; MASS SPECTROMETRY; POLYMERIZATION; PRIORITY JOURNAL; PROTEIN FOLDING;

ALPHA 1-ANTITRYPSIN; CHEMISTRY; HUMANS; HYDROGEN; HYDROGEN-ION CONCENTRATION; KINETICS; MOLECULAR CONFORMATION; POLYMERS; PROTEIN CONFORMATION; PROTEIN DENATURATION; PROTEIN FOLDING; SERPINS; SOLVENTS; TANDEM MASS SPECTROMETRY; THERMODYNAMICS; TRYPTOPHAN;

EID: 84858629624     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1109125109     Document Type: Article

References (23)

1. Gooptu B, Lomas DA (2009) Conformational pathology of the serpins: Themes, variations, and therapeutic strategies. Ann Rev Biochem 78:147-176.
2. Gettins PG (2002) Serpin structure, mechanism, and function. Chem Rev 102:4751-4804.
3. Sivasothy P, Dafforn TR, Gettins PGW, Lomas DA (2000) Pathogenic alpha(1)-antitrypsin polymers are formed by reactive loop-beta-sheet A linkage. J Biol Chem 275:33663-33668.
4. Yamasaki M, Li W, Johnson DJD, Huntington JA (2008) Crystal structure of a stable dimer reveals the molecular basis of serpin polymerization. Nature 455:1255-1265.
5. James EL, Whisstock JC, Gore MG, Bottomley SP (1999) Probing the unfolding pathway of alpha(1)-antitrypsin. J Biol Chem 274:9482-9488.
6. Krishnan B, Gierasch LM (2011) Dynamic local unfolding in the serpin α-1 antitrypsin provides a mechanism for loop insertion and polymerization. Nat Struct Mol Biol 18:222-226.
7. Kim D, Yu MH (1996) Folding pathway of human alpha 1-antitrypsin: Characterization of an intermediate that is active but prone to aggregation. Biochem Biophys Res Commun 226:378-384.
8. Koloczek H, Guz A, Kaszycki P (1996) Fluorescence-detected polymerization kinetics of human alpha-1 antitrypsin. J Protein Chem 15:447-454.
9. Tsutsui Y, Kuri B, Sengupta T, Wintrode PL (2008) The structural basis of serpin polymerization studied by hydrogen/deuterium exchange and mass spectrometry. J Biol Chem 283:30804-30811.
10. Tsutsui Y, Wintrode PL (2007) Cooperative unfolding of a metastable serpin to a molten globule suggests a link between functional and folding energy landscapes. J Mol Biol 371:245-255.
11. Yamasaki M, Sendall TJ, Pearce MC, Whisstock JC, Huntington JA (2011) Molecular basis of alpha-1 antitrypsin deficiency revealed by the structure of a domain swapped trimer. EMBO Rep 12:1011-1017.
12. Onda M, et al. (2008) Cleaved serpin refolds into the relaxed state via a stressed conformer. J Biol Chem 283:17568-17578.
13. Wright HT (1993) Introns and higher-order structure in the evolution of serpins. J Mol Evol 36:136-143.
14. Flaugh SL, Kosinski-Collins MS, King J (2005) Contributions of hydrophobic domain interface interactions to the folding and stability of human gammaD-crystallin. Protein Sci 14:569-581.
15. Lomas DA, et al. (1995) alpha 1-Antitrypsin Mmalton (Phe52-deleted) forms loop-sheet polymers in vivo. Evidence for the C sheet mechanism of polymerization. J Biol Chem 270:16864-16870.
16. Lomas DA, Finch JT, Seyama K, Nukiwa T, Carrell RW (1993) Alpha 1-antitrypsin Siiyama (Ser53 → Phe). Further evidence for intracellular loop-sheet polymerization. J Biol Chem 268:15333-15335.
17. Stein PE, Carrell RW (1995) What do dysfunctional serpins tell us about molecular mobility and disease? Nat Struct Biol 2:96-113.
18. Jung CH, Na YR, Im H (2004) Retarded protein folding of deficient human alpha 1-antitrypsin D256V and L41P variants. Protein Sci 13:694-702.
19. Im H,Woo MS, Hwang KY, YuMH (2002) Interactions causing the kinetic trap in serpin protein folding. J Biol Chem 48:46347-46354.
20. Pearce MC, Cabrita LD, Rubin H, Gore MG, Bottomley SP (2004) Identification of residual structure within denatured antichymotrypsin: Implications for serpin folding and misfolding. Biochem Biophys Res Commun 324:729-735.
21. Dinner AR, Karplus M (2001) The roles of stability and contact order in determining protein folding rates. Nat Struct Mol Biol 8:21-22.
22. Schrödinger, LLC (2010, ) The PyMOL Molecular Graphics System, version 5. (Schrödinger, LLC, New York).
23. Dolmer K, Gettins PG (2012) How the serpin α1-proteinase inhibitor folds. J Biol Chem, 10.1074/jbc.M111.315465.