Zinc Metal Ion Affected the Structural Stability of Amyloid-Like Nanofibrils

Authors

  • Zahraa S. Al-Garawi Physical Biochemistry, Chemistry Departm

DOI:

https://doi.org/10.23851/mjs.v29i3.622

Keywords:

Functional fibrils, amyloids, structural stability, circular dichroism.

Abstract

Synthetic peptides that self-assemble into well-defined structures with a cross-β arrangement are called amyloid-like fibrils. Amyloids are associated with a list of disorders and neuro-degenerative diseases, such as Alzheimer's and Parkinson`s disease. We previously showed that amyloid-like nanofibrils with a repeating motif “IHIH” were functional fibrils. They were able to bind a metal ion through imidazole moieties and mimic the native carbonic anhydrase enzyme by hydrolysing the CO2 molecule. Thus, these synthetic amyloid fibrils were suggest-ed to be good candidates to moderate and update the modern enzymatic molecules. This study aims to shed a light on the stability of these amyloid nanofibrils over a study period of 25 days, in the presence/absence of a metal ion. The work continued for approximately 7 months in the Biochemistry department, School of Life Sciences at the University of Sussex in the United Kingdom. A set of designed peptides with a repeating motif “IHIH” were ex-plored, based on some structural studies. Short and long peptides with free ends as well as closed ends were investigated. Peptides allowed to self-assemble with and without a metal ion (zinc) were then examined using circular dichroism, fluorimetry and electron microscopy for structural biophysical analysis. Regardless of the metal ion contribution, peptides showed stable secondary structures with a -sheet conformation for the incubation time of 25 days. Their morphologies did not appear to change over time. However, the presence of a zinc ion has an effect on the secondary structure of the mature fibrils. Results indicated that fibrils grown with the zinc ion have a significantly higher propensity to form -sheets secondary structures during incubation time. The presence of a zinc ion also affected the dimensions of the amyloid-like fibrils by the end of the study course, at which point they significantly re-duced. This effect of zinc ion on synthetic amyloid fibrils has not been previously reported. The stabilities of the zinc-nanofibrils point to their potential for use in modifying or updating the enzyme-mimic analytical reactions. The effect of adding zinc on the fibrillation seems to be crucial. Although it apparently improved the -sheet assembly, it affected the width/length of the synthetic amyloids. This effect could be promising toward reducing the generation of amyloid fibrils and ultimately understanding the pathogenesis of Alzheimer disease.

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References

Al-Garawi, Z. S., McIntosh, B. A., Neill-Hall, D., Hatimy, A. A., Sweet, S. M., Bagley, M. C. & Serpell, L. C. (2017) The amyloid architecture provides a scaf-fold for enzyme-like catalysts, Na-noscale. 9, 10773-10783.

Andreini, C., Lucia Banci, L., Ivano Ber-tini, I. & Rosato, A. ( 2006) Counting the Zinc-Proteins Encoded in the Human Genome, J Proteome Research. 5, 196-201.

Sousa, S. F., Lopes, A. B., Fernandes, P. A. & Ramos, M. J. (2009) The zinc pro-teome: A tale of stability and functionali-ty., Dalton Trans, 7946–7956.

Butler, A. (1998) Acquisition and utiliza-tion of transitionmetal ions by Marine or-ganisms in Chemistry and Biology of the oceans pp. 207-210, Scince,

Auld, D. S. (2001) Zinc coordination sphere in biochemical zinc sites., BioMet-als. 14, 271-313.

Zastrow, M. L. & Pecoraro, V. L. (2014) Designing hydrolytic zinc metalloen-zymes, Biochemistry. 53, 957-978.

McCall, K. A., Huang, C.-c. & Fierke, C. A. (2000) Function and mechanism of zinc metalloenzymes. in Zinc and health: Current status and future directions pp. 1437S-1446S, Amer Soc Nutrit Sci,

Guler, M. O. & Stupp, S. I. (2007) A Self-assembled nanofiber catalyst for es-ter hydrolysis, J Am Chem Soc. 129, 12082-12083.

Rufo, C. M., Moroz, Y. S., Moroz, O. V., ̈hr, J. S., Smith, T. A., Hu, X., DeGrado, W. F. & Korendovych, I. V. (2014) Short peptides self-assemble to produce catalytic amyloids, Nature Chemistry, Advance online pubilication, 1-7.

Lee, M., Wang, T., Makhlynets, O. V., Wu, Y., Polizzi, N. F., Wu, H., Gosavi, P. M., Stohr, J., Korendovych, I. V., DeGrado, W. F. & Hong, M. (2017) Zinc-binding structure of a catalytic amy-loid from solid-state NMR, Proceedings of the National Academy of Sciences of the United States of America. 114, 6191-6196.

Morris, K. L., Rodger, A., Hicks, M. R., Debulpaep, M., Schymkowitz, J., Rous-seau, F. & Serpell, L. C. (2013) Exploring the sequence-structure relationship for amyloid peptides, The Biochemical jour-nal. 450, 275-83.

Al-Garawi, Z. S., Morris, K. L., Marshall, K. E., Eichler, J. & Serpell, L. C. (2017) The diversity and utility of amyloid fi-brils formed by short amyloidogenic pep-tides, Interface Focus. 7, 20170027.

Kim, S., Kim, J. H., Lee, J. S. & Park, C. B. (2015) Beta-Sheet-Forming, self-assembled peptide nanomaterials towards optical, energy, and healthcare applica-tions, Small J. 11, 3623-3640.

Morris, K. L. & Serpell, L. C. (2012) X-ray fibre diffraction studies of amyloid fibrils, Methods in molecular biology. 849, 121-135.

Knowles, T. P., Vendruscolo, M. & Dob-son, C. M. (2014) The amyloid state and its association with protein misfolding diseases, Nature reviews Molecular cell biology. 15, 384-96.

Pawar, A. P., Dubay, K. F., Zurdo, J., Chiti, F., Vendruscolo, M. & Dobson, C. M. (2005) Prediction of "aggregation-prone" and "aggregation-susceptible" re-gions in proteins associated with neuro-degenerative diseases, Journal of molecu-lar biology. 350, 379-92.

Ryan, D. M. & Nilsson, B. L. (2012) Self-assembled amino acids and dipep-tides as noncovalent hydrogels for tissue engineering, Polym Chem. 3, 18-33.

Lakshmanan, A., Zhang, S. & Hauser, C. A. (2012) Short self-assembling peptides as building blocks for modern nanodevices, Trends in biotechnology. 30, 155-65.

Dehsorkhi, A. & Hamley, I. W. (2014) Silica templating of a self-assembling peptide amphiphile that forms nanotapes, Soft matter. 10, 1660-1664.

Rajagopal, K. & Schneider, J. P. (2004) Self-assembling peptides and proteins for nanotechnological applications, Current opinion in structural biology. 14, 480-486.

Cherny, I. & Gazit, E. (2008) Amyloids: not only pathological agents but also or-dered nanomaterials, Angew Chem Int Ed Engl. 47, 4062-9.

Pilkington, S. M., Roberts, S. J., Meade, S. J. & Gerrard, J. A. (2010) Amyloid fi-brils as a nanoscaffold for enzyme immo-bilization, Biotechnol Prog. 26, 93-100.

Al-Garawi, Z. S., Thorpe, J. R. & Serpell, L. C. (2015) Silica nanowires templated by amyloid-like fibrils, Angew Chem, Int Ed Engl. 54, 13327-13331.

Rufo, C. M., Moroz, Y. S., Moroz, O. V., Stohr, J., Smith, T. A., Hu, X., DeGrado, W. F. & Korendovych, I. V. (2014) Short peptides self-assemble to produce cata-lytic amyloids, Nature chemistry. 6, 303-309.

Al-Garawi, Z. S. (2017) Biophysical-Biochemical structural basis of self-assemble peptides, for bionanotechnolog-ical applications, University of Sussex, United Kingdom.

Knowles, T. P. & Mezzenga, R. (2016) Amyloid fibrils as building blocks for natural and artificial functional materials., Adv Mater. 28, 6546-6561.

Makhlynets, O. V., Gosavi, P. M. & Ko-rendovych, I. V. (2016) Short self-assembling peptides are able to bind to copper and activate oxygen., Angew Chem Int Ed. 55, 9017-9020.

Al-Garawi, Z. S., Kostakis, G. E. & Ser-pell, L. C. (2016) Chemically and ther-mally stable silica nanowires with a β‐sheet peptide core for bionanotechnolo-gy., J Nanobiotechnology. 14, 79-87.

West, M. W., Wang, W., Patterson, J., Mancias, J. D., Beasley, J. R. & Hecht, M. H. (1999) De novo amyloid proteins from designed combinatorial libraries., Proc Natl Acad Sci USA. 96, 11211-11216.

Srivastava, K. R. & Durani, S. (2014) Design of a zinc-finger hydrolase with a synthetic alphabetabeta protein, PloS one. 9, 1-8.

Maynard, C. J., Bush, A. I., Masters, C. L., Cappai, R. & Li, Q.-X. (2005) Metals and amyloid-β in Alzheimer’s disease., Int J Exp Path 86, 147–159.

Abelein, A., Gräslund, A. & Danielsson, J. (2015) Zinc as chaperone-mimicking agent for retardation of amyloid β pep-tide fibril formation., PNAS. 112, 5407–5412.

Fasman, G. D. (1996) Determination of protien secondary structure. in Circular dichroism and the conformational analy-sis of biomolecules (Venyaminov, S. Y. & Yang, J. T., eds) pp. 69-107, Plenum Press, New York.

Marshall, K. E. (2010) Structural poly-morphism of amyloidogenic peptides., Univeristy of Sussex, School of Life Sci-ences.

Munishkina, L. A. & Fink, A. L. (2007) Fluorescence as a method to reveal struc-tures and membrane-interactions of amy-loidogenic proteins., Biochim Biophys Acta. 1768, 1862-85.

Guzow, K., Ganzynkowicz, R., Rzeska, A., Mrozek, J., Szabelski, M., Karolczak, J., Liwo, A. & Wiczk, W. (2004) Photo-physical properties of Tyrosine and Its simple derivatives studied by time-resolved fluorescence spectroscopy, global analysis, and teoretical calcula-tions., J Phys Chem B. 108, 3879-3889.

Lakowicz, J. R. (2007) Protien fluores-cence spectroscopy in Principles of fluo-rescence spectroscopy pp. 534-536, Springer, New Yourk, USA.

Sitkiewicz, E., Oledzki, J., Poznanski, J. & Dadlez, M. (2014) Di-tyrosine cross-link decreases the collisional cross-section of abeta peptide dimers and trimers in the gas phase: An ion mobility study., PloS one. 9, e100200.

van-Maarschalkerweerd, A., Pedersen, M. N., Peterson, H., Nilsson, M., Ngu-yen, T. T. T., Skamris, T., Rand, K., Ve-tri, V., Langkilde, A. E. & Vestergaard, B. (2015) Formation of covalent di-tyrosine dimers in recombinant α-synuclein, Intrins Disord Prot. 3, 1-12.

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Published

10-03-2019

How to Cite

[1]
Z. S. Al-Garawi, “Zinc Metal Ion Affected the Structural Stability of Amyloid-Like Nanofibrils”, Al-Mustansiriyah Journal of Science, vol. 29, no. 3, pp. 50–62, Mar. 2019, doi: 10.23851/mjs.v29i3.622.

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