Symmetry-breaking transitions in the early steps of protein self-assembly

Condorelli, Marcello; Compagnini, Giuseppe; Lolicato, Fabio; Milardi, Danilo; Nhu, Trang; Karttunen, Mikko; Pannuzzo, Martina; Ramamoorthy, Ayyalusamy; Fraternali, Franca; Collu, Francesca; Rézaei, Human; Strodel, Birgit; Raudino, Antonio

doi:10.1007/s00249-020-01424-1

Cited by 31 publications

(29 citation statements)

References 89 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These dual facets of neurotoxicity highlight the major role of trace elements in the pathogenesis of amyloid-associated neurodegenerative diseases. Recently, La Rosa et al exhibited the similarities of oligomerization patterns and structures among hIAPP, AβP and other amyloidogenic proteins using the theoretical model [166]. These similarities in the conformations of various amyloidogenic proteins may strengthen our hypothesis about the common toxic mechanism in amyloidosis.…”

Section: Discussionmentioning

confidence: 87%

Amyloids: Regulators of Metal Homeostasis in the Synapse

2020

View full text Add to dashboard Cite

Conformational changes in amyloidogenic proteins, such as β-amyloid protein, prion proteins, and α-synuclein, play a critical role in the pathogenesis of numerous neurodegenerative diseases, including Alzheimer’s disease, prion disease, and Lewy body disease. The disease-associated proteins possess several common characteristics, including the ability to form amyloid oligomers with β-pleated sheet structure, as well as cytotoxicity, although they differ in amino acid sequence. Interestingly, these amyloidogenic proteins all possess the ability to bind trace metals, can regulate metal homeostasis, and are co-localized at the synapse, where metals are abundantly present. In this review, we discuss the physiological roles of these amyloidogenic proteins in metal homeostasis, and we propose hypothetical models of their pathogenetic role in the neurodegenerative process as the loss of normal metal regulatory functions of amyloidogenic proteins. Notably, these amyloidogenic proteins have the capacity to form Ca2+-permeable pores in membranes, suggestive of a toxic gain of function. Therefore, we focus on their potential role in the disruption of Ca2+ homeostasis in amyloid-associated neurodegenerative diseases.

show abstract

Section: Discussionmentioning

confidence: 87%

Amyloids: Regulators of Metal Homeostasis in the Synapse

2020

View full text Add to dashboard Cite

show abstract

“…They are able to form β-barrels in contrast to the α-helices of almost all other membrane proteins. The association of monomers within native trimer is stabilized through the hydrophobic and hydrophilic interaction at the subunit interface and involves 35% of the barrel surface area [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Porin from Marine Bacterium Marinomonas primoryensis KMM 3633T: Isolation, Physico-Chemical Properties, and Functional Activity

et al. 2020

View full text Add to dashboard Cite

Marinomonas primoryensis KMM 3633T, extreme living marine bacterium was isolated from a sample of coastal sea ice in the Amursky Bay near Vladivostok, Russia. The goal of our investigation is to study outer membrane channels determining cell permeability. Porin from M. primoryensis KMM 3633T (MpOmp) has been isolated and characterized. Amino acid analysis and whole genome sequencing were the sources of amino acid data of porin, identified as Porin_4 according to the conservative domain searching. The amino acid composition of MpOmp distinguished by high content of acidic amino acids and low content of sulfur-containing amino acids, but there are no tryptophan residues in its molecule. The native MpOmp existed as a trimer. The reconstitution of MpOmp into black lipid membranes demonstrated its ability to form ion channels whose conductivity depends on the electrolyte concentration. The spatial structure of MpOmp had features typical for the classical gram-negative porins. However, the oligomeric structure of isolated MpOmp was distinguished by very low stability: heat-modified monomer was already observed at 30 °C. The data obtained suggest the stabilizing role of lipids in the natural membrane of marine bacteria in the formation of the oligomeric structure of porin.

show abstract

“…Recently, a theoretical model, supported by extensive molecular dynamics simulations and experiments, has been developed. It is based on the description of the intrinsic asymmetry in protein aggregates using models of field theory [153]. In its most straightforward formulation, the theory considers a linear aggregate of polypeptides (proteins), which can have different conformational states, and interact through intermolecular forces that depend on the internal conformational states.…”

Section: Symmetry-breaking Transitions Of Oligomers Self-assemblingmentioning

confidence: 99%

“…For 30 years, plenty of biophysics studies on IDPs have been published, and it has been shown that this family of proteins share many physical-chemical characteristics. Although they have different amino acid sequences, they show very similar dynamics and structural behaviors; indeed, they have also been named chameleonic [153,166] proteins. In an aqueous solution, they form non-crystalline-structured aggregates, rich in beta-sheet structures, penetrate model membranes by forming pores, and damage the membrane with a mechanism described as detergent-like.…”

Section: Common Features Apparent Irreproducibility and Paradoxes Amentioning

confidence: 99%

“…This process can be theoretically predicted considering the energy scenario related to the system, particularly the patterned array of ordered and disordered conformers, originating from a configurational instability. The symmetry-breaking theory justifies not only the self-assembling into an oligomeric structure, but also the behavior of multimeric proteins [153].…”

Section: Common Features Apparent Irreproducibility and Paradoxes Amentioning

confidence: 99%

See 1 more Smart Citation

Amyloidogenic Intrinsically Disordered Proteins: New Insights into Their Self-Assembly and Their Interaction with Membranes

Scollo

Raudino

2020

Life

Self Cite

View full text Add to dashboard Cite

Aβ, IAPP, α-synuclein, and prion proteins belong to the amyloidogenic intrinsically disordered proteins’ family; indeed, they lack well defined secondary and tertiary structures. It is generally acknowledged that they are involved, respectively, in Alzheimer’s, Type II Diabetes Mellitus, Parkinson’s, and Creutzfeldt–Jakob’s diseases. The molecular mechanism of toxicity is under intense debate, as many hypotheses concerning the involvement of the amyloid and the toxic oligomers have been proposed. However, the main role is represented by the interplay of protein and the cell membrane. Thus, the understanding of the interaction mechanism at the molecular level is crucial to shed light on the dynamics driving this phenomenon. There are plenty of factors influencing the interaction as mentioned above, however, the overall view is made trickier by the apparent irreproducibility and inconsistency of the data reported in the literature. Here, we contextualized this topic in a historical, and even more importantly, in a future perspective. We introduce two novel insights: the chemical equilibrium, always established in the aqueous phase between the free and the membrane phospholipids, as mediators of protein-transport into the core of the bilayer, and the symmetry-breaking of oligomeric aggregates forming an alternating array of partially ordered and disordered monomers.

show abstract

Symmetry-breaking transitions in the early steps of protein self-assembly

Cited by 31 publications

References 89 publications

Amyloids: Regulators of Metal Homeostasis in the Synapse

Amyloids: Regulators of Metal Homeostasis in the Synapse

Porin from Marine Bacterium Marinomonas primoryensis KMM 3633T: Isolation, Physico-Chemical Properties, and Functional Activity

Amyloidogenic Intrinsically Disordered Proteins: New Insights into Their Self-Assembly and Their Interaction with Membranes

Contact Info

Product

Resources

About