Zinc Metal Ion Affected the Structural Stability of Amyloid-Like Nanofibrils
Keywords:Functional fibrils, amyloids, structural stability, circular dichroism.
AbstractSynthetic 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.
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.
How to Cite
Articles accepted for publication in Al-Mustansiriyah Journal of Science (MJS) are protected under the Creative Commons Attribution 4.0 International License (CC-BY-NC). Authors of accepted articles are requested to sign a copyright release form prior to their article being published. All authors must agree to the submission, sign copyright release forms, and agree to be included in any correspondence between MJS and the authors before submitting a work to MJS. For personal or educational use, permission is given without charge to print or create digital copies of all or portions of a MJS article. However, copies must not be produced or distributed for monetary gain. It is necessary to respect the copyright of any parts of this work that are not owned by MJS.