Morphology and Persistence Length of Amyloid Fibrils Are Correlated to Peptide Molecular Structure

vandenAkker, Corianne C.; Engel, M.F.M.; Velikov, Krassimir P.; Bonn, Mischa; Koenderink, Gijsje H.

doi:10.1021/ja206513r

Cited by 117 publications

(125 citation statements)

References 40 publications

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“…4C and D). These short protofibrillar structures, compatible with the helicoidal ␤-spine observed along the crystal c axis, are often observed in prefibrillar wormlike amyloid oligomers (54,55).…”

Section: Resultssupporting

confidence: 57%

“…4). Therefore, the ␤-spine arrangement observed in the crystal packing of 2B sol molecules likely reflects the organization adopted by 2B proteins in HAV-infected cells, adding to the growing number of proteins with the ability to self-assemble into functional amyloid-like structures (35,52,55,63,64). Moreover, the ability of the HAV 2B protein to bind microsomal membranes seems to be related to the presence of a putative transmembrane helix located at the C-terminal end of the protein, which is predicted to start 30 residues downstream of the sequence of the present crystallographic structure (30).…”

Section: Discussionmentioning

confidence: 99%

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Structural Basis for Host Membrane Remodeling Induced by Protein 2B of Hepatitis A Virus

Vives-Adrián

Garriga

Buxaderas

et al. 2015

J Virol

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The complexity of viral RNA synthesis and the numerous participating factors require a mechanism to topologically coordinate and concentrate these multiple viral and cellular components, ensuring a concerted function. Similarly to all other positivestrand RNA viruses, picornaviruses induce rearrangements of host intracellular membranes to create structures that act as functional scaffolds for genome replication. The membrane-targeting proteins 2B and 2C, their precursor 2BC, and protein 3A appear to be primarily involved in membrane remodeling. Little is known about the structure of these proteins and the mechanisms by which they induce massive membrane remodeling. Here we report the crystal structure of the soluble region of hepatitis A virus (HAV) protein 2B, consisting of two domains: a C-terminal helical bundle preceded by an N-terminally curved five-stranded antiparallel ␤-sheet that displays striking structural similarity to the ␤-barrel domain of enteroviral 2A proteins. Moreover, the helicoidal arrangement of the protein molecules in the crystal provides a model for 2B-induced host membrane remodeling during HAV infection. IMPORTANCENo structural information is currently available for the 2B protein of any picornavirus despite it being involved in a critical process in viral factory formation: the rearrangement of host intracellular membranes. Here we present the structure of the soluble domain of the 2B protein of hepatitis A virus (HAV). Its arrangement, both in crystals and in solution under physiological conditions, can help to understand its function and sheds some light on the membrane rearrangement process, a putative target of future antiviral drugs. Moreover, this first structure of a picornaviral 2B protein also unveils a closer evolutionary relationship between the hepatovirus and enterovirus genera within the Picornaviridae family. Due to their limited genome size, viruses are obligate intracellular parasites that recruit cell host components for their multiplication. All currently known positive-strand RNA viruses, as well as some DNA viruses, rearrange host intracellular membranes to create the so-called viral factories, vesicular structures that concentrate the viral and host proteins required for replication as well as the viral genomes and, at the same time, shield them from host antiviral defenses (1).Despite the key role of viral factories in viral replication, the molecular processes leading to their formation are only partially understood. This is especially true for picornaviruses (PVs), one of the largest families of pathogens known, for which the lack of information on host membrane rearrangement processes contrasts with the highly detailed data available for other stages of the picornavirus viral cycle (e.g., receptor binding, viral entry, and RNA synthesis).The Picornaviridae family includes many important human and animal pathogens such as polioviruses, rhinoviruses, footand-mouth disease virus, and hepatitis A virus (HAV). HAV is the only species and only serotype in t...

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Section: Resultssupporting

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Structural Basis for Host Membrane Remodeling Induced by Protein 2B of Hepatitis A Virus

Vives-Adrián

Garriga

Buxaderas

et al. 2015

J Virol

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“…Although WPI is a mixture of different proteins, previous studies have shown that PNFs formed under the applied conditions are built from β-lactoglobulin-derived peptides (24). Interestingly, vandenAkker et al demonstrated that pure β-lactoglobulin can assemble into fibrils with different morphology depending on the initial protein concentration (10). In their study, low protein concentration (3%) resulted in long and straight fibrils whereas short, worm-like structures were formed at higher concentrations (7.5%).…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, the straight fibrils have an apparent height of 4.1 ± 1.1 nm whereas the curved fibrils are thinner (2.5 ± 0.5 nm). Assuming that the straight fibrils are built from 2-3 protofilaments, as described by others (10,25), and that these filaments have the same cross-sectional area as the curved fibrils, we can get an estimate of the relative elastic moduli of the two classes of PNFs. The straight fibrils then appear to have an elastic modulus that is 15-25× higher than the curved fibrils.…”

Section: Resultsmentioning

confidence: 99%

Flow-assisted assembly of nanostructured protein microfibers

Kamada

Mittal

Söderberg

et al. 2017

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

115

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Some of the most remarkable materials in nature are made from proteins. The properties of these materials are closely connected to the hierarchical assembly of the protein building blocks. In this perspective, amyloid-like protein nanofibrils (PNFs) have emerged as a promising foundation for the synthesis of novel bio-based materials for a variety of applications. Whereas recent advances have revealed the molecular structure of PNFs, the mechanisms associated with fibril-fibril interactions and their assembly into macroscale structures remain largely unexplored. Here, we show that whey PNFs can be assembled into microfibers using a flow-focusing approach and without the addition of plasticizers or cross-linkers. Microfocus small-angle X-ray scattering allows us to monitor the fibril orientation in the microchannel and compare the assembly processes of PNFs of distinct morphologies. We find that the strongest fiber is obtained with a sufficient balance between ordered nanostructure and fibril entanglement. The results provide insights in the behavior of protein nanostructures under laminar flow conditions and their assembly mechanism into hierarchical macroscopic structures.protein nanofibrils | amyloid | hierarchical assembly | flow focusing | small-angle X-ray scattering P roteins are widely used in nature to create high-performance materials that can have both extraordinary mechanical properties (similar to muscles, silks) and sophisticated functionalities (e.g., adhesion, biological signaling) (1). The characteristics of these materials are intimately connected to the hierarchical assembly of the protein building blocks with well-defined organization at all structural levels (2). Improved knowledge about how to control the assembly of protein molecules into higher-order structures would open the possibilities to create novel bio-based materials for a variety of applications. In this perspective, the ability of protein molecules to undergo nonnative self-assembly into protein nanofibrils (PNFs) with highly organized supramolecular structures is of significant interest (3). The formation of PNFs was initially observed in association with diseases, such as Alzheimer's and Parkinson's diseases, and type II diabetes, where human organs are impaired by fibrous protein inclusions referred to as amyloid (4). However, several non-disease-related proteins have also been shown to form amyloid-like fibrils, e.g., the bovine whey protein β-lactoglobulin (5), hen-egg lysozyme (6), and soybean proteins (7). The unique fibrous structures of PNFs have the potential for being the building block of protein-based nanomaterials and to be used as scaffolds for applications such as tissue engineering, drug delivery systems, and biosensors (3). PNFs are characterized by intermolecular β-sheet structures, where the peptide backbones are oriented perpendicularly to the fibril axis and connected through a network of hydrogen bonds (4,8). This provides them with stiffness equivalent to silk and strength comparable to steel (2, 8). Moreo...

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“…This is normally done in PM-IRRAS and SFG by observing the amide bands, which are known to be shifted to higher wavenumbers when the structure changes from β-sheet to α-helices. VandenAkker et al [109] reported changes in secondary structure of amyloid fibrils by following the changes in the amide I band in SFG measurements. Fig.…”

Section: Cell Membrane Modelsmentioning

confidence: 99%

Vibrational spectroscopy for probing molecular-level interactions in organic films mimicking biointerfaces

Volpati

Aoki

Aléssio

et al. 2014

Advances in Colloid and Interface Science

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Morphology and Persistence Length of Amyloid Fibrils Are Correlated to Peptide Molecular Structure

Cited by 117 publications

References 40 publications

Structural Basis for Host Membrane Remodeling Induced by Protein 2B of Hepatitis A Virus

Structural Basis for Host Membrane Remodeling Induced by Protein 2B of Hepatitis A Virus

Flow-assisted assembly of nanostructured protein microfibers

Vibrational spectroscopy for probing molecular-level interactions in organic films mimicking biointerfaces

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