Micro-heterogeneity and aggregation in β2-microglobulin solutions: effects of temperature, pH, and conformational variant addition
- 117 Downloads
- 23 Citations
Abstract
We show that β2-microglobulin solutions in physiological conditions contain a tiny fraction of aggregates, which can hardly be filtered out and tend to re-form spontaneously. At physiological pH the fractional amount and size distribution of the latter aggregates do not depend on temperature. Conversely, in the pH range typical of the peri-articular tissue acidosis that often occurs in hemodialysis, temperature increase leads to fast and irreversible growth of the aggregates. Quite similar, but strongly enhanced aggregation effects can be induced even in physiological conditions by adding a very small amount of ΔN6, a naturally occurring truncated isoform of β2-m known to promote fibrillogenesis.
Keywords
Fibril Dynamic Light Scattering Dynamic Light Scattering Carpal Tunnel Syndrome Hydrodynamic RadiusNotes
Acknowledgements
This work has been supported by grants from the Italian Ministries of Health (Grant n.08920301) and of Instruction, University, and Research (MIUR, PRIN 2003 n.2003051399 and FIRB RBNEO1S29H).
References
- Berne A, Pecora R (1976) Dynamic light scattering. Wiley, New YorkGoogle Scholar
- Chiti F, De Lorenzi E, Grossi S, Mangione P, Giorgetti S, Caccialanza G, Dobson CM, Merlini G, Ramponi G, Bellotti V (2001) J Biol Chem 276:46714–46721CrossRefGoogle Scholar
- Connors LH, Shirahama T, Skinner M, Fenves A, Cohen AS (1985) Biochem Biophys Res Commun 13:1063–1068CrossRefGoogle Scholar
- Corazza A, Pettirossi F, Viglino P, Verdone G, Garcia J, Dumy P, Giorgetti S, Mangione P, Raimondi S, Stoppini M, Bellotti V, Esposito G (2004) J Biol Chem 279:9176–9189CrossRefGoogle Scholar
- Dobson CM (1997) Nature 426(6968):884–890CrossRefADSGoogle Scholar
- Drueke TB (2000) Nephrol Dial Transplant 15:17–24Google Scholar
- Esposito G, Michelutti R, Verdone G, Viglino P, Hernandez H, Robinson CV, Amoresano A, Dal Piaz F, Monti M, Pucci P, Mangione P, Stoppini M, Merlini G, Ferri G, Bellotti V (2000) Protein Sci 5:831–845CrossRefGoogle Scholar
- Gordon J, Wu CH, Rastegar M, Safa AR (2003) Int J Cancer 103:316–327CrossRefGoogle Scholar
- Kovacic V, Roguljic L, Kovacic V (2003) Am J Nephrol 23:158–164CrossRefGoogle Scholar
- Lambert MP, Barlow AK, Chromy BA, Edwards C, Freed R, Liosatos M, Morgan TE, Rozovsky I, Trommer B, Viola KL et al (1995) Proc Natl Acad Sci USA 95:6448–6453CrossRefADSGoogle Scholar
- Lomakin A, Chung DS, Benedek GB, Kirkschner DA, Teplow DB (1996) Proc Natl Acad Sci USA 93:1125–1129CrossRefADSGoogle Scholar
- Mattson MP, Goodman Y (1995) Brain Res 676:219–224CrossRefGoogle Scholar
- McParland VJ, Kad NM, Kalverda AP, Brown A, Kirwin-Jones P, Hunter MG, Sunde M, Radford SE (2000) Biochemistry 39:8735–8746CrossRefGoogle Scholar
- Merlini G, Bellotti V (2003) N Engl J Med 349:583–596CrossRefGoogle Scholar
- Naiki H, Hashimoto N, Suzuki S, Kimura H, Nakakuki K, Gejyo F (1997) Amyloid Int J Exp Clin Invest 4:223–232Google Scholar
- Olofsson A, Ostman J, Lundgren E (2002) Clin Chem Lab Med 40:1266–1270CrossRefGoogle Scholar
- Pertosa G, Grandaliano G, Gesualdo L, Schena FP (2000) Kidney Int Suppl 76:S104–S111CrossRefGoogle Scholar
- Piazza R, Peyre V, Degiorgio V (1998) Phys Rev E 58:R2733–R2736CrossRefADSGoogle Scholar
- Rosano C, Zuccotti S, Mangione P, Giorgetti S, Bellotti V, Pettirossi F, Corazza A, Viglino P, Esposito G, Bolognesi M (2004) J Mol Biol 335:1051–1064CrossRefGoogle Scholar
- Schwalbe S, Holzhauer M, Schaeffer J, Galanski M, Koch KM, Floege J (1997) Kidney Int 52:1077–1083CrossRefGoogle Scholar
- Serio TR, Cashikar AG, Kowal AS, Sawicki GJ, Moslehi JJ, Serpell L, Arnsdorf MF, Lindquist SL (1996) Science 289:1317–1321CrossRefADSGoogle Scholar
- Soreghan B, Kosmoski J, Glabe C (1995) J Biol Chem 269:28551–28554Google Scholar
- Verdone G, Corazza A, Viglino P, Pettirossi F, Giorgetti S, Mangione P, Andreola A, Stoppini M, Bellotti V, Esposito G (2002) Protein Sci 11:487–499CrossRefGoogle Scholar
- Villanueva J, Hoshino M, Katou H, Kardos J, Hasegawa K, Naiki H, Goto Y (2004) Protein Sci 13:797–809CrossRefGoogle Scholar
- Ward TT, Steigbigel RT (1978) Am J Med 64:933–936Google Scholar