Micelle‐Triggered β‐Hairpin to α‐Helix Transition in a 14‐Residue Peptide from a Choline‐Binding Repeat of the Pneumococcal Autolysin LytA

Zamora-Carreras, Héctor; Maestro, Beatríz; Strandberg, Erik; Ulrich, Anne S.; Sanz, Jesús M.; Jiménez, M.

doi:10.1002/chem.201500447

Cited by 16 publications

(77 citation statements)

References 65 publications

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“…In contrastt ot he absence of any secondary structural tendency shownb ym ost chameleon sequences, predictions for the LytA 239-252 sequence show ab ias for b-hairpin formation. [4] Moreover,t he observed peptide conformation dependso nt he solventc onditions, and not on the protein con-text. Therefore, LytA 239-252 can be described as aconformational switch.…”

Section: Introductionmentioning

confidence: 93%

“…Ribbonrepresentations of A) the b-hairpin and B) the a-helix formedb ypeptide LytA 239-252 in aqueous solution andint he presence of micelles, respectively. [4] Aromatic (F,Y ,W)a nd aliphatic (I, A) residues are in green,p olar residues (T,N )incyan, Lysi nblue, and Asp in red. [239][240][241][242][243][244][245][246][247][248][249][250][251][252] in aqueouss olutiona nd in the presence of detergent micelles,r espectively, [4] and putative for the designed LytA 239-252 variants.…”

Section: Peptide Variants Designmentioning

confidence: 99%

“…[4] Aromatic (F,Y ,W)a nd aliphatic (I, A) residues are in green,p olar residues (T,N )incyan, Lysi nblue, and Asp in red. [239][240][241][242][243][244][245][246][247][248][249][250][251][252] in aqueouss olutiona nd in the presence of detergent micelles,r espectively, [4] and putative for the designed LytA 239-252 variants. In the b-hairpin schemes,h ydrogenb onds are indicated by vertical lines, residues at non-hydrogen bond sites are underlined, and turn residues are markedi nbold.S ide-chains for residues at non-hydrogenbonded sitespointtowards the same b-sheet face (face 1), and those at hydrogen-bonded sites towards the opposite face (face 2).…”

Section: Peptide Variants Designmentioning

confidence: 99%

“…On the whole, the profiles of conformational shifts indicatet hat they form b-hairpin structures in aqueous solution, similart ot he wild-type peptide LytA 239-252 . [4] The negative Dd Ha values for I6 and K9 in the variant K3W5-LytA 239-252 might suggest that this variant has some geometricaldifferences at the turn region relative to the wild-type peptide.F urthera nd stronger evidence about b-hairpin formation in the two peptides comesf rom the sets of nonsequentialN OEs. In b-hairpins, the nonsequential NOEs involving side chain protons can be classified into two subsets,o ne for each face of the b-hairpin.…”

Section: Conformational Study In Aqueous Solutionmentioning

confidence: 99%

“…In this context, we have recently describedt he folding of a 14-mer peptide( LytA 239-252 ), corresponding to the hairpin core of aC BR from the pneumococcal LytA autolysin. [4] This peptide forms av ery stable, native-like b-hairpin in aqueous solution and is transformedi nto an a-helix in the presence of detergent micelles and in small unilamellar phospholipidv esicles ( Figure 1). In contrastt ot he absence of any secondary structural tendency shownb ym ost chameleon sequences, predictions for the LytA 239-252 sequence show ab ias for b-hairpin formation.…”

Section: Introductionmentioning

confidence: 99%

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Roles of Amphipathicity and Hydrophobicity in the Micelle‐Driven Structural Switch of a 14‐mer Peptide Core from a Choline‐Binding Repeat

Zamora-Carreras

Maestro

Strandberg

et al. 2018

Chemistry A European J

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Choline‐binding repeats (CBRs) are ubiquitous sequences with a β‐hairpin core that are found in the surface proteins of several microorganisms such as S. pneumoniae (pneumococcus). Previous studies on a 14‐mer CBR sequence derived from the pneumoccal LytA autolysin (LytA239–252 peptide) have demonstrated a switch behaviour for this peptide, so that it acquires a stable, native‐like β‐hairpin conformation in aqueous solution but is reversibly transformed into an amphipathic α‐helix in the presence of detergent micelles. With the aim of understanding the factors responsible for this unusual β‐hairpin to α‐helix transition, and to specifically assess the role of peptide hydrophobicity and helical amphipathicity in the process, we designed a series of LytA239–252 variants affecting these two parameters and studied their interaction with dodecylphosphocholine (DPC) micelles by solution NMR, circular dichroism and fluorescence spectroscopies. Our results indicate that stabilising cross‐strand interactions become essential for β‐hairpin stability in the absence of optimal turn sequences. Moreover, both amphipathicity and hydrophobicity display comparable importance for helix stabilisation of CBR‐derived peptides in micelles, indicating that these sequences represent a novel class of micelle/membrane‐interacting peptides.

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Section: Introductionmentioning

confidence: 93%

Section: Peptide Variants Designmentioning

confidence: 99%

Section: Peptide Variants Designmentioning

confidence: 99%

Section: Conformational Study In Aqueous Solutionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Roles of Amphipathicity and Hydrophobicity in the Micelle‐Driven Structural Switch of a 14‐mer Peptide Core from a Choline‐Binding Repeat

Zamora-Carreras

Maestro

Strandberg

et al. 2018

Chemistry A European J

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Turncoat Polypeptides: We Adapt to Our Environment

et al. 2019

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A common interpretation of Anfinsen's hypothesis states that one amino acid sequence should fold into a single, native, ordered state, or a highly similar set thereof, coinciding with the global minimum in the folding‐energy landscape, which, in turn, is responsible for the function of the protein. However, this classical view is challenged by many proteins and peptide sequences, which can adopt exchangeable, significantly dissimilar conformations that even fulfill different biological roles. The similarities and differences of concepts related to these proteins, mainly chameleon sequences, metamorphic proteins, and switch peptides, which are all denoted herein “turncoat” polypeptides, are reviewed. As well as adding a twist to the conventional view of protein folding, the lack of structural definition adds clear versatility to the activity of proteins and can be used as a tool for protein design and further application in biotechnology and biomedicine.

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Design of Functional Globular β‐Sheet Miniproteins

Pham,

Thomas

2024

ChemBioChem

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The design of discrete β‐sheet peptides is far less advanced than e.g. the design of α‐helical peptides. The reputation of β‐sheet peptides as being poorly soluble and aggregation‐prone often hinders active design efforts. Here, we show that this reputation is unfounded. We demonstrate this by looking at the β‐hairpin and WW domain. Their structure and folding have been extensively studied and they have long served as model systems to investigate protein folding and folding kinetics. The resulting fundamental understanding has led to the development of hyperstable β‐sheet scaffolds that fold at temperatures of 100°C or high concentrations of denaturants. These have been used to design functional miniproteins with protein or nucleic acid binding properties, in some cases with such success that medical applications are conceivable. The β‐sheet scaffolds are not always completely rigid, but can be specifically designed to respond to changes in pH, redox potential or presence of metal ions. Some engineered β‐sheet peptides also exhibit catalytic properties, although not comparable to those of natural proteins. Previous reviews have focused on the design of stably folded and nonaggregating β‐sheet sequences. In our review, we now also address design strategies to obtain functional miniproteins from β‐sheet folding motifs.

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Micelle‐Triggered β‐Hairpin to α‐Helix Transition in a 14‐Residue Peptide from a Choline‐Binding Repeat of the Pneumococcal Autolysin LytA

Cited by 16 publications

References 65 publications

Roles of Amphipathicity and Hydrophobicity in the Micelle‐Driven Structural Switch of a 14‐mer Peptide Core from a Choline‐Binding Repeat

Roles of Amphipathicity and Hydrophobicity in the Micelle‐Driven Structural Switch of a 14‐mer Peptide Core from a Choline‐Binding Repeat

Turncoat Polypeptides: We Adapt to Our Environment

Design of Functional Globular β‐Sheet Miniproteins

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