De novo design of fibrils made of short α-helical coiled coil peptides

Potekhin, Sergey A.; Melnik, Tatiana N.; Попов, В. И.; Lanina, N. F.; Vazina, A.A.; Rigler, Per; Verdini, A. S.; Corradin, Giampietro; Kajava, Andrey V.

doi:10.1016/s1074-5521(01)00073-4

Cited by 156 publications

(182 citation statements)

References 36 publications

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“…This unexpected mimicry in a relatively simple and designed binary peptide system is intriguing and may shed light on both natural and synthetic self-assembly processes in general. In comparison to other designed ␣-helix-based fibers, the SAFs display considerably more order in their assembled structures (7,17,46); although we note longitudinal stripes are observed by TEM in one system (38), and hexagonal packing of helical fibrils has also been demonstrated by WAX in another (12). In addition, because ours is a dual-peptide system, whereas the others rely on just one peptide to self-assemble, we have more control over the assembly process (42).…”

Section: Resultsmentioning

confidence: 65%

“…Predominantly, such work has used ␤-structured peptides that form amyloid-like structures (3, 5, 6, 10). Relatively less has been attempted with ␣-helix-based assemblies, however (7,(11)(12)(13)(14). The development of ␣-helical systems would provide useful comparisons with the more-explored amyloid-like systems and also allows the application of the considerable body of protein design and engineering knowledge for ␣-helical structures and assemblies (15)(16)(17).…”

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confidence: 99%

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Engineering nanoscale order into a designed protein fiber

Papapostolou

Smith

Atkins

et al. 2007

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

238

250

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We have established a designed system comprising two peptides that coassemble to form long, thickened protein fibers in water. This system can be rationally engineered to alter fiber assembly, stability, and morphology. Here, we show that rational mutations to our original peptide designs lead to structures with a remarkable level of order on the nanoscale that mimics certain natural fibrous assemblies. In the engineered system, the peptides assemble into two-stranded ␣-helical coiled-coil rods, which pack in axial register in a 3D hexagonal lattice of size 1.824 nm, and with a periodicity of 4.2 nm along the fiber axis. This model is supported by both electron microscopy and x-ray diffraction. Specifically, the fibers display surface striations separated by nanoscale distances that precisely match the 4.2-nm length expected for peptides configured as ␣-helices as designed. These patterns extend unbroken across the widths (>50 nm) and lengths (>10 m) of the fibers. Furthermore, the spacing of the striations can be altered predictably by changing the length of the peptides. These features reflect a high level of internal order within the fibers introduced by the peptidedesign process. To our knowledge, this exceptional order, and its persistence along and across the fibers, is unique in a biomimetic system. This work represents a step toward rational bottom-up assembly of nanostructured fibrous biomaterials for potential applications in synthetic biology and nanobiotechnology.bionanoscience ͉ nanofibers ͉ peptide assembly ͉ rational protein design ͉ self-assembly

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Section: Resultsmentioning

confidence: 65%

mentioning

confidence: 99%

Engineering nanoscale order into a designed protein fiber

Papapostolou

Smith

Atkins

et al. 2007

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

238

250

View full text Add to dashboard Cite

show abstract

“…For example, these filamentous nanostructures could be formed fromhelical peptides with 25-50 amino acids [87]. The -helical peptides with 2-5 helices can aggregate around each other to form nanofibers [88,89]. These -helical peptides can also self-assemble into nanofibers using around 30-amino-acidlong peptides through helical coiled-coils structures [90].…”

Section: -Helical Peptidementioning

confidence: 99%

Peptide Self-Assembled Nanostructures for Drug Delivery Applications

Fan

Shen

et al. 2017

Journal of Nanomaterials

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Peptide self-assembled nanostructures are very popular in many biomedical applications. Drug delivery is one of the most promising applications among them. The tremendous advantages for peptide self-assembled nanostructures include good biocompatibility, low cost, tunable bioactivity, high drug loading capacities, chemical diversity, specific targeting, and stimuli responsive drug delivery at disease sites. Peptide self-assembled nanostructures such as nanoparticles, nanotubes, nanofibers, and hydrogels have been investigated by many researchers for drug delivery applications. In this review, the underlying mechanisms for the self-assembled nanostructures based on peptides with different types and structures are introduced and discussed. Peptide self-assembled nanostructures associated promising drug delivery applications such as anticancer drug and gene drug delivery are highlighted. Furthermore, peptide self-assembled nanostructures for targeted and stimuli responsive drug delivery applications are also reviewed and discussed.

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“…All conformations can be clustered in four familiess -sheet, R-helix/coil, 3 10 -helix/ coil, and coil/coilswith populations of 1.5, 0.4, 0.0, and 98.1%, respectively, at 253 K and of 0.0, 1.5, 0.2, and 98.3%, respectively, at 317.6 K. These results show that, irrespective of the temperature, a seven-residue peptide is not sufficient to encode R-helical coiled coils, in agreement with the observation that these structures are formed by peptides with 25-50 amino acids. 86 They also indicate that this peptide has a very low probability to stabilize into a dimeric -sheet, in contrast to A (16)(17)(18)(19)(20)(21)(22), where REMD-OPEP predictions suggest a percentage of -strand content of 36% at 310 K for the dimer. …”

mentioning

confidence: 99%

“…Although this seven-residue peptide does not exist in nature, it is one repeat (abcdefg, containing hydrophobic residues at positions a and d and polar residues generally elsewhere) used by proteins to form R-helical coiled coil structures. 86 In addition, it shares the same amino acid length as the Alzheimer's fragment A (16)(17)(18)(19)(20)(21)(22) known to form amyloid fibrils in vitro. 87 Therefore, this peptide represents an ideal system to demonstrate that OPEP, used to study protein aggregation, is not biased toward the formation of -sheets.…”

mentioning

confidence: 99%

Replica Exchange Molecular Dynamics Simulations of Coarse-grained Proteins in Implicit Solvent

et al. 2008

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Current approaches aimed at determining the free energy surface of all-atom medium-size proteins in explicit solvent are slow and are not sufficient to converge to equilibrium properties. To ensure a proper sampling of the configurational space, it is preferable to use reduced representations such as implicit solvent and/or coarsegrained protein models, which are much lighter computationally. Each model must be verified, however, to ensure that it can recover experimental structures and thermodynamics. Here we test the coarse-grained implicit solvent OPEP model with replica exchange molecular dynamics (REMD) on six peptides ranging in length from 10 to 28 residues: two alanine-based peptides, the second -hairpin from protein G, the Trp-cage and zinc-finger motif, and a dimer of a coiled coil peptide. We show that REMD-OPEP recovers the proper thermodynamics of the systems studied, with accurate structural description of the -hairpin and Trp-cage peptides (within 1-2 Å from experiments). The light computational burden of REMD-OPEP, which enables us to generate many hundred nanoseconds at each temperature and fully assess convergence to equilibrium ensemble, opens the door to the determination of the free energy surface of larger proteins and assemblies.

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De novo design of fibrils made of short α-helical coiled coil peptides

Abstract: The fact that the peptide assembles in an expected fibril arrangement demonstrates the credibility of our conception of design. The discovery of a short peptide with fibril-forming ability and stimulus-sensitive behavior opens new opportunities for a number of applications.

Cited by 156 publications

References 36 publications

Engineering nanoscale order into a designed protein fiber

Engineering nanoscale order into a designed protein fiber

Peptide Self-Assembled Nanostructures for Drug Delivery Applications

Replica Exchange Molecular Dynamics Simulations of Coarse-grained Proteins in Implicit Solvent

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