Kinetics of Insulin Aggregation: Disentanglement of Amyloid Fibrillation from Large-Size Cluster Formation

Manno, Mauro; Craparo, Emanuela Fabiola; Martorana, Vincenzo; Bulone, Donatella; Biagio, Pier Luigi San

doi:10.1529/biophysj.105.077636

Cited by 68 publications

(77 citation statements)

References 28 publications

(54 reference statements)

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“…The kinetic profiles of fiber formation by full-length IAPP, A␤, insulin, and the mammalian prion show that fiber-dependent nucleation plays a prominent role (9,10,12,14). Similarly, the stochastic reaction kinetics reported for insulin, A␤, and huntingtin can be rationalized with 2°nucleation (10,14,36).…”

Section: Discussionmentioning

confidence: 82%

“…Historically, hemoglobin S was the first biological polymerization reaction to demonstrate a transition time that is much shorter than its preceding lag phase (8). This same phenomenon is commonly reported for amyloid systems including islet amyloid polypeptide (IAPP) from type II diabetes (9), A␤ from Alzheimer's (10), PrP from the mammalian prion (11), and Sup35 from the yeast prion (12,13), as well as model systems such as insulin (14). In such instances, a secondary (2°or fiber-dependent) mechanism of nucleation, in addition to the primary (1°or fiber-independent) one, is invoked to describe the kinetic profile.…”

mentioning

confidence: 67%

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Fiber-dependent amyloid formation as catalysis of an existing reaction pathway

Ruschak¹,

Miranker

2007

Proc. Natl. Acad. Sci. U.S.A.

203

251

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A central component of a number of degenerative diseases is the deposition of protein as amyloid fibers. Self-assembly of amyloid occurs by a nucleation-dependent mechanism that gives rise to a characteristic sigmoidal reaction profile. The abruptness of this transition is a variable characteristic of different proteins with implications to both chemical mechanism and the aggressiveness of disease. Because nucleation is defined as the rate-limiting step, we have sought to determine the nature of this step for a model system derived from islet amyloid polypeptide. We show that nucleation occurs by two pathways: a fiber-independent (primary) pathway and a fiber-dependent (secondary) pathway. We first show that the balance between primary and secondary contributions can be manipulated by an external interface. Specifically, in the presence of this interface, the primary mechanism dominates, whereas in its absence, the secondary mechanism dominates. Intriguingly, we determine that both the reaction order and the enthalpy of activation of the two nucleation processes are identical. We interrogate this coincidence by global analysis using a simplified model generally applicable to protein polymerization. A physically reasonable set of parameters can be found to satisfy the coincidence. We conclude that primary and secondary nucleation need not represent different processes for amyloid formation. Rather, they are alternative manifestations of the same, surfacecatalyzed nucleation event.amylin ͉ fibers ͉ islet amyloid polypeptide ͉ nucleation T he noncovalent, fibrous self-assembly of proteins, including hemoglobin S, actin, microtubules, and amyloid fibers, occurs by a nucleation-dependent mechanism (1-5). If polymer product formation is monitored as a function of time in a reaction where all of the protein is initially monodisperse, there is a lag phase in which little product is formed, followed by a period of rapid growth (2). Such observations are consistent with a rate-limiting step in which change occurs to a high-energy intermediate known as the nucleus. In many systems such as actin, collagen, and microtubules, the nucleus is modeled as an oligomeric species that is in a highly unfavorable equilibrium with monomer (1, 3-6). The nucleus may also be a high-energy conformation of monomer, such as that reported for polyglutamine (7). Regardless, the rate-limiting step involves a nucleus because it is defined as the species with the highest free energy and therefore lowest population (1, 4).This model of nucleation alone cannot account for the high apparent cooperativity of conversion observed in many systems. Historically, hemoglobin S was the first biological polymerization reaction to demonstrate a transition time that is much shorter than its preceding lag phase (8). This same phenomenon is commonly reported for amyloid systems including islet amyloid polypeptide (IAPP) from type II diabetes (9), A␤ from Alzheimer's (10), PrP from the mammalian prion (11), and Sup35 from the yeast prion (12, 13), as well as mode...

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Section: Discussionmentioning

confidence: 82%

mentioning

confidence: 67%

Fiber-dependent amyloid formation as catalysis of an existing reaction pathway

Ruschak¹,

Miranker

2007

Proc. Natl. Acad. Sci. U.S.A.

203

251

View full text Add to dashboard Cite

show abstract

“…41,[85][86][87][88][89][90][91] There is a wealth of experimental evidence of the nucleation-enhancing properties of surfaces of insulin amyloid fibrils (e.g., Jansen et al 41 ). The existence of the secondary nucleation pathway has twofold consequences.…”

Section: Discussionmentioning

confidence: 99%

Vortex-Induced Formation of Insulin Amyloid Superstructures Probed by Time-Lapse Atomic Force Microscopy and Circular Dichroism Spectroscopy

Loksztejn

Dzwolak

2010

Journal of Molecular Biology

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“…• C) [89,90]. Glucagon [91] and islet amyloid polypeptide [92] also aggregate on tantalum oxide coated quartz surfaces and mica surfaces, respectively.…”

Section: Indirect Evidences Of Material-induced Protein Conformationamentioning

confidence: 99%

Protein conformational changes induced by adsorption onto material surfaces: an important issue for biomedical applications of material science

Ballet¹,

Boulangé²,

Bréchet³

et al. 2010

Bulletin of the Polish Academy of Sciences: Technical Sciences

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Abstract. Protein adsorption on solid surfaces is a widespread phenomenon of large biological and biotechnological significance. Conformational changes are likely to accompany protein adsorption, but are difficult to evidence directly. Nevertheless they have important consequences, since the partial unfolding of protein domains can expose hitherto hidden amino acids. This remodeling of the protein surface can trigger the activation of molecular complexes such as the blood coagulation cascade or the innate immune complement system. In the case of extracellular matrix, it can also change the way cells interact with the material surfaces and result in modified cell behavior. In this review, we present direct and indirect evidences that support the view that some proteins change their conformation upon adsorption. We also show that both physical and chemical methods are needed to study the extent and kinetics of protein conformational changes. In particular, AFM techniques and cryo-electron microscopy provide useful and complementary information. We then review the chemical and topological features of both proteins and material surfaces in relation with protein adsorption. Mutating key amino acids in proteins changes their stability and this is related to material-induced conformational changes, as shown for instance with insulin. In addition, combinatorial methods should provide valuable information about peptide or antibody adsorption on well-defined material surfaces. These techniques could be combined with molecular modeling methods to decipher the rules governing conformational changes associated with protein adsorption.

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Kinetics of Insulin Aggregation: Disentanglement of Amyloid Fibrillation from Large-Size Cluster Formation

Cited by 68 publications

References 28 publications

Fiber-dependent amyloid formation as catalysis of an existing reaction pathway

Fiber-dependent amyloid formation as catalysis of an existing reaction pathway

Vortex-Induced Formation of Insulin Amyloid Superstructures Probed by Time-Lapse Atomic Force Microscopy and Circular Dichroism Spectroscopy

Protein conformational changes induced by adsorption onto material surfaces: an important issue for biomedical applications of material science

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