Structural basis for mutation-induced destabilization of profilin 1 in ALS

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

Volumn 112, Issue 26, 2015, Pages 7984-7989

  Boopathy, Sivakumar ^a   Silvas, Tania V ^a   Tischbein, Maeve ^a   Jansen, Silvia ^b   Shandilya, Shivender M ^a   Zitzewitz, Jill A ^a   Landers, John E ^a   Goode, Bruce L ^b   Schiffer, Celia A ^a   Bosco, Daryl A ^a  

^a UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL   (United States)

^b BRANDEIS UNIVERSITY   (United States)

Author keywords

Amyotrophic lateral sclerosis; Profilin 1; Protein misfolding; Protein stability; X ray crystallography

Indexed keywords

PROFILIN; PROFILIN 1; UNCLASSIFIED DRUG; PFN1 PROTEIN, HUMAN;

AMYOTROPHIC LATERAL SCLEROSIS; ARTICLE; CELL INCLUSION; CONFORMATIONAL TRANSITION; CONTROLLED STUDY; CRYSTAL STRUCTURE; ESCHERICHIA COLI; GENE MUTATION; IN VITRO STUDY; LOSS OF FUNCTION MUTATION; NERVE CELL; NONHUMAN; PRIORITY JOURNAL; PROTEIN METABOLISM; X RAY CRYSTALLOGRAPHY; CELL LINE; CHEMISTRY; GENETICS; HUMAN; METABOLISM; MUTATION; PROTEIN CONFORMATION; PROTEIN FOLDING;

AMYOTROPHIC LATERAL SCLEROSIS; CELL LINE; CRYSTALLOGRAPHY, X-RAY; HUMANS; MUTATION; NEURONS; PROFILINS; PROTEIN CONFORMATION; PROTEIN FOLDING;

EID: 84937958012     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1424108112     Document Type: Article

References (52)

1. Smith BN, et al. (2015) Novel mutations support a role for Profilin 1 in the pathogenesis of ALS. Neurobiol Aging 36(3):1602.e17-1602.e27.
2. Wu CH, et al. (2012) Mutations in the profilin 1 gene cause familial amyotrophic lateral sclerosis. Nature 488(7412):499-503.
3. Bosco DA, LaVoie MJ, Petsko GA, Ringe D (2011) Proteostasis and movement disorders: Parkinson's disease and amyotrophic lateral sclerosis. Cold Spring Harb Perspect Biol 3(10):a007500.
4. Witke W (2004) The role of profilin complexes in cell motility and other cellular processes. Trends Cell Biol 14(8):461-469.
5. Lambrechts A, et al. (1997) The mammalian profilin isoforms display complementary affinities for PIP2 and proline-rich sequences. EMBO J 16(3):484-494.
6. Winklhofer KF, Tatzelt J, Haass C (2008) The two faces of protein misfolding: Gain- and loss-of-function in neurodegenerative diseases. EMBO J 27(2):336-349.
7. Figley MD, Bieri G, Kolaitis RM, Taylor JP, Gitler AD (2014) Profilin 1 associates with stress granules and ALS-linked mutations alter stress granule dynamics. J Neurosci 34(24):8083-8097.
8. Austin JA, et al. (2014) Disease causing mutants of TDP-43 nucleic acid binding domains are resistant to aggregation and have increased stability and half-life. Proc Natl Acad Sci USA 111(11):4309-4314.
9. Rotunno MS, Bosco DA (2013) An emerging role for misfolded wild-type SOD1 in sporadic ALS pathogenesis. Front Cell Neurosci 7:253.
10. Watanabe S, Kaneko K, Yamanaka K (2013) Accelerated disease onset with stabilized familial amyotrophic lateral sclerosis (ALS)-linked mutant TDP-43 proteins. J Biol Chem 288(5):3641-3654.
11. Eriksson AE, et al. (1992) Response of a protein structure to cavity-creating mutations and its relation to the hydrophobic effect. Science 255(5041):178-183.
12. Joerger AC, Ang HC, Fersht AR (2006) Structural basis for understanding oncogenic p53 mutations and designing rescue drugs. Proc Natl Acad Sci USA 103(41):15056-15061.
13. Yue P, Li Z, Moult J (2005) Loss of protein structure stability as a major causative factor in monogenic disease. J Mol Biol 353(2):459-473.
14. Fratta P, et al. (2014) Profilin1 E117G is a moderate risk factor for amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 85(5):506-508.
15. Vedadi M, et al. (2006) Chemical screening methods to identify ligands that promote protein stability, protein crystallization, and structure determination. Proc Natl Acad Sci USA 103(43):15835-15840.
16. Ringe D, Petsko GA (2009) What are pharmacological chaperones and why are they interesting? J Biol 8(9):80.
17. Verhoef LG, Lindsten K, Masucci MG, Dantuma NP (2002) Aggregate formation inhibits proteasomal degradation of polyglutamine proteins. Hum Mol Genet 11(22):2689-2700.
18. Myers JK, Pace CN, Scholtz JM (1995) Denaturant m values and heat capacity changes: relation to changes in accessible surface areas of protein unfolding. Protein Sci 4(10):2138-2148.
19. Rotunno MS, et al. (2014) Identification of a misfolded region in superoxide dismutase1 that is exposed in amyotrophic lateral sclerosis. J Biol Chem 289(41):28527-28538.
20. Fedorov AA, Pollard TD, Almo SC (1994) Purification, characterization and crystallization of human platelet profilin expressed in Escherichia coli. J Mol Biol 241(3):480-482.
21. Ferron F, Rebowski G, Lee SH, Dominguez R (2007) Structural basis for the recruitment of profilin-actin complexes during filament elongation by Ena/VASP. EMBO J 26(21):4597-4606.
22. Mahoney NM, Rozwarski DA, Fedorov E, Fedorov AA, Almo SC (1999) Profilin binds proline-rich ligands in two distinct amide backbone orientations. Nat Struct Biol 6(7):666-671.
23. Prabu-Jeyabalan M, Nalivaika EA, Romano K, Schiffer CA (2006) Mechanism of substrate recognition by drug-resistant human immunodeficiency virus type 1 protease variants revealed by a novel structural intermediate. J Virol 80(7):3607-3616.
24. Cedergren-Zeppezauer ES, et al. (1994) Crystallization and structure determination of bovine profilin at 2.0 A resolution. J Mol Biol 240(5):459-475.
25. Chik JK, Lindberg U, Schutt CE (1996) The structure of an open state of beta-actin at 2.65 A resolution. J Mol Biol 263(4):607-623.
26. Hájková L, Björkegren Sjögren C, Korenbaum E, Nordberg P, Karlsson R (1997) Characterization of a mutant profilin with reduced actin-binding capacity: Effects in vitro and in vivo. Exp Cell Res 234(1):66-77.
27. Korenbaum E, et al. (1998) The role of profilin in actin polymerization and nucleotide exchange. Biochemistry 37(26):9274-9283.
28. Porta JC, Borgstahl GE (2012) Structural basis for profilin-mediated actin nucleotide exchange. J Mol Biol 418(1-2):103-116.
29. Schutt CE, Myslik JC, Rozycki MD, Goonesekere NC, Lindberg U (1993) The structure of crystalline profilin-beta-actin. Nature 365(6449):810-816.
30. Sohn RH, Chen J, Koblan KS, Bray PF, Goldschmidt-Clermont PJ (1995) Localization of a binding site for phosphatidylinositol 4,5-bisphosphate on human profilin. J Biol Chem 270(36):21114-21120.
31. Suetsugu S, Miki H, Takenawa T (1998) The essential role of profilin in the assembly of actin for microspike formation. EMBO J 17(22):6516-6526.
32. Björkegren C, Rozycki M, Schutt CE, Lindberg U, Karlsson R (1993) Mutagenesis of human profilin locates its poly(L-proline)-binding site to a hydrophobic patch of aromatic amino acids. FEBS Lett 333(1-2):123-126.
33. Ostrander DB, Ernst EG, Lavoie TB, Gorman JA (1999) Polyproline binding is an essential function of human profilin in yeast. Eur J Biochem 262(1):26-35.
34. Pollard TD, Cooper JA (1984) Quantitative analysis of the effect of Acanthamoeba profilin on actin filament nucleation and elongation. Biochemistry 23(26):6631-6641.
35. Eriksson AE, Baase WA, Wozniak JA, Matthews BW (1992) A cavity-containing mutant of T4 lysozyme is stabilized by buried benzene. Nature 355(6358):371-373.
36. Ling SC, et al. (2010) ALS-associated mutations in TDP-43 increase its stability and promote TDP-43 complexes with FUS/TLS. Proc Natl Acad Sci USA 107(30):13318-13323.
37. Dillen L, et al. (2013) Explorative genetic study of UBQLN2 and PFN1 in an extended Flanders-Belgian cohort of frontotemporal lobar degeneration patients. Neurobiol Aging 34(6):1711.e1-1711.e5.
38. van Blitterswijk M, et al. (2013) Profilin-1 mutations are rare in patients with amyotrophic lateral sclerosis and frontotemporal dementia. Amyotroph Lateral Scler Frontotemporal Degener 14(5-6):463-469.
39. Tiloca C, et al. (2013) Screening of the PFN1 gene in sporadic amyotrophic lateral sclerosis and in frontotemporal dementia. Neurobiol Aging 34(5):1517.e9-1517.e10.
40. Yang S, et al. (2013) Mutation analysis and immunopathological studies of PFN1 in familial and sporadic amyotrophic lateral sclerosis. Neurobiol Aging 34(9):2235.e7-2235.e10.
41. Rotty JD, et al. (2015) Profilin-1 serves as a gatekeeper for actin assembly by Arp2/3-dependent and -independent pathways. Dev Cell 32(1):54-67.
42. Palmer I, Wingfield PT (2012) Preparation and extraction of insoluble (inclusion-body) proteins from Escherichia coli. Curr Protoc Protein Sci Chap 6, Unit 6.3.
43. Bilsel O, Yang L, Zitzewitz JA, Beechem JM, Matthews CR (1999) Time-resolved fluorescence anisotropy study of the refolding reaction of the alpha-subunit of tryptophan synthase reveals nonmonotonic behavior of the rotational correlation time. Biochemistry 38(13):4177-4187.
44. Greene RF, Jr, Pace CN (1974) Urea and guanidine hydrochloride denaturation of ribonuclease, lysozyme, alpha-chymotrypsin, and beta-lactoglobulin. J Biol Chem 249(17):5388-5393.
45. Mackness BC, Tran MT, McClain SP, Matthews CR, Zitzewitz JA (2014) Folding of the RNA recognition motif (RRM) domains of the amyotrophic lateral sclerosis (ALS)-linked protein TDP-43 reveals an intermediate state. J Biol Chem 289(12):8264-8276.
46. Winter G (2010) xia2: An expert system for macromolecular crystallography data reduction. J Appl Cryst 43:186-190.
47. Kabsch W (2010) Xds. Acta Crystallogr D Biol Crystallogr 66(Pt 2):125-132.
48. McCoy AJ, et al. (2007) Phaser crystallographic software. J Appl Cryst 40(Pt4):658-674.
49. Emsley P, Cowtan K (2004) Coot: Model-building tools for molecular graphics. Acta Crystallogr D Biol Crystallogr 60(Pt 12 Pt 1):2126-2132.
50. Adams PD, et al. (2010) PHENIX: A comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr D Biol Crystallogr 66(Pt 2):213-221.
51. Murshudov GN, Vagin AA, Dodson EJ (1997) Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr D Biol Crystallogr 53(Pt 3):240-255.
52. Lu J, Pollard TD (2001) Profilin binding to poly-L-proline and actin monomers along with ability to catalyze actin nucleotide exchange is required for viability of fission yeast. Mol Biol Cell 12(4):1161-1175.