Structure-based design of peptides that self-assemble into regular polyhedral nanoparticles

Raman, Senthil Kumar; Machaidze, Gia; Lustig, Ariel; Aebi, Ueli; Burkhard, Peter

doi:10.1016/j.nano.2006.04.007

Cited by 174 publications

(201 citation statements)

References 36 publications

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“…Detailed knowledge of the folding mechanisms of coiled coils is crucial for exploiting their potential in a wide range of applications and understanding their functions in a large number of biological processes (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(21)(22)(23)(24). Here, we use the GCN4 leucine zipper as a model system to investigate fundamental principles underlying coiled-coil formation.…”

Section: Discussionmentioning

confidence: 99%

“…The secondary 13 C␣ chemical shifts of the peptide averaged over residues His-18 to Lys-28 indicate a progressive loss of ␣-helix structure from Ϸ60% at neutral pH to Ͻ10% with decreasing pH (Fig. 2 A).…”

Section: A Network Of Interactions Stabilizes the Helical Structure Omentioning

confidence: 99%

“…To test the hypothesis that multiple charged groups contribute to the ␣-helix-stabilizing network of the trigger peptide, we further characterized the pH dependence of helical structure in p16-31 by following 1 H␣ and 13 C␣ chemical shifts in 10 1 H-13 C heteronuclear single quantum correlation (HSQC) spectra collected between pH 1.5 and 12.5. The secondary 13 C␣ chemical shifts of the peptide averaged over residues His-18 to Lys-28 indicate a progressive loss of ␣-helix structure from Ϸ60% at neutral pH to Ͻ10% with decreasing pH (Fig.…”

Section: A Network Of Interactions Stabilizes the Helical Structure Omentioning

confidence: 99%

“…A need for a detailed understanding of coiled-coil folding is relevant, particularly in light of the important functions these structures play in almost all biological processes, as well as the considerable attention coiled coils have recently garnered in a wide range of applications, including basic research, nanomaterials, protein engineering, biotechnology, and medicine (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). Furthermore, understanding the folding mechanisms of coiled coils is of fundamental interest to experimentalists and theoreticians challenged by the question of how the sequence of a protein defines its specific 3D structure.…”

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confidence: 99%

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Molecular basis of coiled-coil formation

Steinmetz

Jelesarov

Matousek

et al. 2007

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

125

129

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Coiled coils have attracted considerable interest as design templates in a wide range of applications. Successful coiled-coil design strategies therefore require a detailed understanding of coiled-coil folding. One common feature shared by coiled coils is the presence of a short autonomous helical folding unit, termed ''trigger sequence,'' that is indispensable for folding. Detailed knowledge of trigger sequences at the molecular level is thus key to a general understanding of coiled-coil formation. Using a multidisciplinary approach, we identify and characterize here the molecular determinants that specify the helical conformation of the monomeric early folding intermediate of the GCN4 coiled coil. We demonstrate that a network of hydrogen-bonding and electrostatic interactions stabilize the trigger-sequence helix. This network is rearranged in the final dimeric coiled-coil structure, and its destabilization significantly slows down GCN4 leucine zipper folding. Our findings provide a general explanation for the molecular mechanism of coiled-coil formation.autonomous folding unit ͉ protein folding ͉ trigger sequence ͉ leucine zipper ͉ ␣-helix A lthough coiled coils have been used traditionally as model systems for protein folding studies, the molecular basis of how they fold is still largely unknown. A need for a detailed understanding of coiled-coil folding is relevant, particularly in light of the important functions these structures play in almost all biological processes, as well as the considerable attention coiled coils have recently garnered in a wide range of applications, including basic research, nanomaterials, protein engineering, biotechnology, and medicine (1-13). Furthermore, understanding the folding mechanisms of coiled coils is of fundamental interest to experimentalists and theoreticians challenged by the question of how the sequence of a protein defines its specific 3D structure. Along these lines, we have been interested particularly in coiled-coil ''trigger sequences,'' which encode stable monomeric ␣-helices that are indispensable for coiled-coil formation (14-18). Although there are a few examples of synthetic peptides that fold either into heterodimers (19) or at conditions of extremes of pH (20) without an apparent trigger sequence, the ''trigger site'' concept is generally accepted because these short autonomous helical folding units are structurally and functionally conserved in a large number of native coiled-coil proteins (reviewed in refs. 21-24). Detailed knowledge of the properties of trigger sequences at the molecular level is therefore key to an understanding of coiled-coil formation and function in general.The parallel two-stranded leucine zipper of the yeast transcriptional activator GCN4 is the best-characterized coiled coil and thus represents an excellent paradigm for a comprehensive analysis of the roles of trigger sequences in coiled-coil folding. Our current understanding of the folding kinetics of the GCN4 leucine zipper is based on extensive stopped-flow studies and te...

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Section: Discussionmentioning

confidence: 99%

Section: A Network Of Interactions Stabilizes the Helical Structure Omentioning

confidence: 99%

Section: A Network Of Interactions Stabilizes the Helical Structure Omentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Molecular basis of coiled-coil formation

Steinmetz

Jelesarov

Matousek

et al. 2007

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

125

129

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“…81 To integrate and capitalize on the abovementioned features more effectively, Raman et al have used computer modeling to design self-assembling peptide nanoparticles (SAPNs). 82 As a result, SAPNs as small as 16 nm can be designed. Allowance can thus be made to present epitopes on the surface of the SAPNs, which in turn equip the SAPNs to home in on their targets.…”

mentioning

confidence: 99%

Harnessing supramolecular peptide nanotechnology in biomedical applications

Chan

Lee

Zhuo

et al. 2017

IJN

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The harnessing of peptides in biomedical applications is a recent hot topic. This arises mainly from the general biocompatibility of peptides, as well as from the ease of tunability of peptide structure to engineer desired properties. The ease of progression from laboratory testing to clinical trials is evident from the plethora of examples available. In this review, we compare and contrast how three distinct self-assembled peptide nanostructures possess different functions. We have 1) nanofibrils in biomaterials that can interact with cells, 2) nanoparticles that can traverse the bloodstream to deliver its payload and also be bioimaged, and 3) nanotubes that can serve as cross-membrane conduits and as a template for nanowire formation. Through this review, we aim to illustrate how various peptides, in their various self-assembled nanostructures, possess great promise in a wide range of biomedical applications and what more can be expected.

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