Rational Design of a Reversible pH-Responsive Switch for Peptide Self-Assembly

Zimenkov, Yuri; Dublin, Steven N.; Ni, Rong; Tu, Raymond S.; Breedveld, Victor; Apkarian, Robert P.; Conticello, Vincent P.

doi:10.1021/ja0605974

Cited by 184 publications

(167 citation statements)

References 21 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: 66%

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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: 66%

“…Other groups have described longitudinal stripes on negatively stained images of designed fibers (37,38) and natural proteins (39). It is important to emphasize the second-and thirdgeneration SAFs show identical striation patterns upon positive and negative staining.…”

Section: Resultsmentioning

confidence: 96%

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

“…Coiled-coil designs have been described in which oligomerization has been coupled to events such as metal binding (46), a redox environment (47), and pH changes (48). Such programmability could be introduced into the design to make cage assembly and disassembly responsive to environmental conditions or specific ligands.…”

Section: Discussionmentioning

confidence: 99%

Flexible, symmetry-directed approach to assembling protein cages

Sciore

Koldewey

et al. 2016

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

135

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The assembly of individual protein subunits into large-scale symmetrical structures is widespread in nature and confers new biological properties. Engineered protein assemblies have potential applications in nanotechnology and medicine; however, a major challenge in engineering assemblies de novo has been to design interactions between the protein subunits so that they specifically assemble into the desired structure. Here we demonstrate a simple, generalizable approach to assemble proteins into cage-like structures that uses short de novo designed coiled-coil domains to mediate assembly. We assembled eight copies of a C 3 -symmetric trimeric esterase into a well-defined octahedral protein cage by appending a C 4 -symmetric coiled-coil domain to the protein through a short, flexible linker sequence, with the approximate length of the linker sequence determined by computational modeling. The structure of the cage was verified using a combination of analytical ultracentrifugation, native electrospray mass spectrometry, and negative stain and cryoelectron microscopy. For the protein cage to assemble correctly, it was necessary to optimize the length of the linker sequence. This observation suggests that flexibility between the two protein domains is important to allow the protein subunits sufficient freedom to assemble into the geometry specified by the combination of C 4 and C 3 symmetry elements. Because this approach is inherently modular and places minimal requirements on the structural features of the protein building blocks, it could be extended to assemble a wide variety of proteins into structures with different symmetries.coiled coils | protein design | native mass spectrometry | analytical ultracentrifugation | cryoelectron microscopy

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“…[280] Conticello et al arbeiteten dieses Modell weiter aus [281] und bauten durch Austausch dreier Isoleucinreste durch Histidin einen reversiblen pH-empfindlichen Auslçser der Selbstorganisation innerhalb des hydrophoben Kerns ein. [282] Diese Konfiguration ermçglichte auch eine selektive ioneninduzierte Fibrillenassoziation. [283,284] Anstatt sich auf die zufällige Stapelung von Homooligomeren zu verlassen, konstruierten Woolfson et al ein gestapeltes Heterodimer, das eine Doppelwendel-Struktur bildet und dabei Überhänge ("sticky ends") aufweist, um die Barriere zu weiterer "Coiled-Coil"-Assoziation beim Vorliegen glatter Enden ("blunt ends") zu überwinden (Abbildung 14).…”

Section: Hierarchische A-helix-basierte Materialienunclassified

Modulares Design in natürlichen und biomimetischen elastischen Materialien

Kushner

Guan

2011

Angewandte Chemie

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Unter Verwendung der zwanzig natürlichen Aminosäuren als Grundbausteine haben biologische Systeme während der Jahrmillionen unter evolutionärem und umweltbedingtem Druck stabile und leichte Peptid‐basierte Materialien entwickelt. Diese Materialien übertreffen ihre synthetischen Gegenstücke in mehrfacher Hinsicht: 1) Multifunktionalität/Abstimmbarkeit, 2) Anpassungsfähigkeit/Reizempfindlichkeit, 3) Synthese und Weiterverarbeitung bei Umgebungsbedingungen in wässrigem Medium und 4) Wiederverwertung und biologische Abbaubarkeit. Diese besonderen Eigenschaften können durch eine “Bottom‐up”‐Synthese und die hierarchische Organisation auf verschiedenen Längenskalen erreicht werden. Das Arbeitsgebiet der “Biomimikry” beschäftigt sich damit, die Gestaltungsprinzipien natürlicher Materialien und deren molekulare Bausteine aufzuklären und zu kopieren. Hier beschreiben wir, was bereits über Struktur und molekulare Mechanismen natürlicher polymerer Materialien erforscht wurde, sowie den Fortschritt in Richtung synthetischer “Nachbildungen” dieser bemerkenswerten Systeme.

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Rational Design of a Reversible pH-Responsive Switch for Peptide Self-Assembly

Cited by 184 publications

References 21 publications

Engineering nanoscale order into a designed protein fiber

Engineering nanoscale order into a designed protein fiber

Flexible, symmetry-directed approach to assembling protein cages

Modulares Design in natürlichen und biomimetischen elastischen Materialien

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