Abstract
The amyloid β-peptide (Aβ) is a major component of insoluble amyloid deposits in Alzheimer’s disease, and the ability of the β-peptide to exist in different conformations is dependent on residues 1–28 [β-(1–28)]. However, different from humans, no Aβ amyloid deposition has been found in aged rats’ brains. Studying the three-dimensional solution structure of rat Aβ-(1–28) and the binding circumstance of Zn2+ is beneficial to a clear understanding of the potential role of Zn2+ in Alzheimer-associated neuropathogenesis and to suggest why there is no amyloid deposition in aged rats’ brains. Here we used nuclear magnetic resonance (NMR) spectroscopy to determine the solution structure of rat Aβ-(1–28) and the binding constant of Zn2+ to rat Aβ-(1–28). Our results suggest that (1) the three-dimensional solution structure of rat Aβ-(1–28) is more stable than that of human Aβ-(1–28) in DMSO-d 6 and that a helical region from Glu16 to Val24 exists in the rat Aβ-(1–28); (2) the affinity of Zn2+ for rat Aβ-(1–28) is lower than that for human Aβ-(1–28) and the NMR data suggest that Arg13, His6, and His14 residues provide the primary binding sites for Zn2+; and (3) the proper binding of Zn2+ to rat Aβ-(1–28) can induce the peptide to change to a more stable conformation.
Similar content being viewed by others
Abbreviations
- Aβ:
-
amyloid β-peptide
- AD:
-
Alzheimer’s disease
- hAβ-(1–28):
-
human Aβ-(1–28)
- rAβ-(1-28):
-
rat Aβ-(1–28)
- REM:
-
restrained energy minimization
References
Roher AE, Lowenson JD, Clarke S, Wolkow C, Wang R, Cotter RJ, Reardon IM, Zürcher-Neely HA, Heinrikson RL, Ball MJ, Greenberg BD (1993) J Biol Chem 268:3072–3083
Pike CJ, Burdick D, Walencewicz AJ, Glabd CG, Cotman CW (1993) J Neurosci 13:1676–1687
Lorenzo A, Yankner BA (1994) Proc Natl Acad Sci USA 91:12243–12247
Pike CJ, Walencewicz AJ, Glabe CG, Cotman CW (1991) Eur J Pharmacol 207:367–368
Barrow CJ, Zagorski MG (1991) Science 235:179–182
Haass C, Schlossmacher MG, Hung AY, Vigo-Pelfrey C, Mellon A, Ostaszewski BL, Lieberburg I, Koo EH, Schenk D, Teplow DB, Selkoe DJ (1992) Nature 359:322–325
Seubert P, Vigo-Pelfrey C, Esch F, Lee M, Dovey H, Davis DL, Shina S, Schlossmacher M, Whaley J, Swindlehurst C, McCormack R, Wolfert R, Bryant K, Lieberburg I, Schenk D (1992) Nature 359:325–327
Shoji M, Golde TE, Ghiso J, Cheung TT, Estus S, Shaffer LN, Cai XD, McKay DM, Tintner R, Frangione B, Younkin SG (1992) Science 258:126–129
Kelly JW (1998) Curr Opin Struct Biol 8:101–106
Rochet JC, Lansbury PT (2000) Curr Opin Struct Biol 10:60–68
Johnstone EM, Chaney MO, Norris FH, Pascual R, Little SP (1991) Mol Brain Res 10:299–305
Shivers BD, Hilbich C, Multhaup G, Salbaum M, Beyreuther K, Seeburg PH (1988) EMBO J 7:1365–1370
Bush AI, Pettingell WH, Multhaup G, Paradis M, Vonsattel JP, Gussella JF, Beyreuther K, Masters CL, Tanzi RE (1994) Science 265:1464–1467
Liu S, Howlett G, Barrow CJ (1999) Biochemistry 38:9373–9378
Zagorski MG, Barrow CJ (1992) Biochemistry 31:5621–5631
Talafous J, Marcinowski KJ, Klopman G, Zagorski MG (1994) Biochemistry 33:7788–7796
Sorimachi K, Craik DJ (1994) Eur J Biochem 219:237–251
Temussi PA, Tancredi T, Pastore A, Castiglione-Morelli MA (1987) Biochemistry 26:7856–7863
Temussi PA, Picone D, Castiglione-Morelli MA, Motta A, Tancredi T (1989) Biopolymers 28:91–107
Wynants C, Van-Binst G, Lossli HR (1985) Int J Pept Protein Res 25:608–614
Wynants C, Van-Binst G, Lossli HR (1985) Int J Pept Protein Res 25:615–621
Amodeo P, Motta A, Picone D, Saviano G, Tancredi T, Temussi PA (1991) J Magn Reson 95:201–207
Huang X, Cuajungco MP, Atwood CS, Moir RD, Tanzi RE, Bush AI (2000) J Nutr 130:1488s–1492s
Jeener J, Meier BH, Bachmann P, Ernst RR (1979) J Chem Phys 71:4546–4553
Wüthrich K (1986) NMR of proteins and nucleic acids. Wiley, New York
Bruker (2000) XWINNMR, version 2.6. Bruker, Rheinstetten
Eccles C, Günter P, Billeter M, Wüthrich K (1991) J Biomol NMR 1:111–130
Günter P, Braun W, Wüthrich K (1991) J Mol Biol 217:517–530
Günter P, Mumenthaler XXXX, Wüthrich K (1997) J Mol Biol 273:283–298
Pearlman DA, Case DA, Caldwell JW, Ross WS, Cheatham TE, Ferguson DM, Seibel GL, Singh UC, Weiner PK, Kollman PA (1997) AMBER 5.0. University of California, San Francisco
Laskowski RA, Rullmann JAC, MacArthur MW, Kaptein R, Thornton JM (1996) J Biomol NMR 8:477–486
Laskowski RA, MacArthur MW, Moss DS, Thornton JM (1993) J Appl Crystallogr 26:283–291
Soto C, Castaño EM, Frangione B, Inestrosa NC (1995) J Biol Chem 270:3063–3067
Baily PJ, Pace S (2001) Coord Chem Rev 214:91–141
Ratilla EMA, Kostic NM (1988) J Am Chem Soc 110:4427–4428
Ratilla EMA, Scott BK, Moxness MS, Kostic NM (1990) Inorg Chem 29:918–926
Aoki S, Iwaida K, Hanamoto N, Shiro M, Kimura E (2002) J Am Chem Soc 124:5256–5257
Fielding L (2003) Curr Top Med Chem 3:39–53
Espinosa JF, Asensio JL, García JL, Laynez J, Bruix M, Wright C, Siebert HC, Gabius HJ, Cañada FJ, Jiménez-Barbero J (2000) Eur J Biochem 267:3965–3978
Asensio JL, Siebert HC, von der Lieth CW, Laynez J, Bruix M, Soedjanaamadja UM, Beintema JJ, Cañada FJ, Gabius HJ, Jiménez-Barbero J (2000) Proteins 40:218–236
Bush AI, Pettingell WH, Paradis MD, Tanzi RE (1994) J Biol Chem 269:12152–12158
Kozin SA, Zirah S, Rebuffat S, Hoa GHB, Debey P (2001) Biochem Biophys Res Commun 285:959–964
Curtain CC, Ali F, Volitakis I, Cherny RA, Norton RS, Beyreuther K, Barrow CJ, Master CL, Bush AI, Barnham KJ (2001) J Biol Chem 276:20466–20473
Miura T, Suzuki K, Kohata N, Takeuchi H (2000) Biochemistry 39:7024–7031
Choo L-PI, Wetzel DL, Halliday WC, Jackson M, LeVine SM, Mantsch HH (1996) Biophys J 71:1672–1679
Malinchik SB, Inouye H, Szumowski KE, Kirschner DA (1998) Biophys J 74:537–545
Acknowledgements
This work is supported by the National Natural Science Foundation of China.
Author information
Authors and Affiliations
Corresponding author
Electronic Supplementary Material
Rights and permissions
About this article
Cite this article
Huang, J., Yao, Y., Lin, J. et al. The solution structure of rat Aβ-(1–28) and its interaction with zinc ion: insights into the scarcity of amyloid deposition in aged rat brain. J Biol Inorg Chem 9, 627–635 (2004). https://doi.org/10.1007/s00775-004-0556-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00775-004-0556-x