Effect of a single aspartate on helix stability at different positions in a neutral alanine‐based peptide

Huyghues-Despointes, Beatrice M. P.; Scholtz, J. Martin; Baldwin, Robert L.

doi:10.1002/pro.5560021006

Cited by 141 publications

(157 citation statements)

References 31 publications

(50 reference statements)

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“…Interestingly, then, these observations mirror the fraying behavior at the ends of helices that has been reported for isolated, short helical peptides. 23,24 Under conditions very far from unfolding, most amide HX may be ascribed to local fluctuations, which likely involve breaking individual hydrogen bonds. Such reactions occur very infrequently.…”

Section: Resultsmentioning

confidence: 99%

“…This predicted end-fraying effect is analogous to the behavior observed for short monomeric peptides. 23,24 Such peptides show a distribution of helical and non-helical conformations, with the central residues having the highest probability of being helical, while the ends fray. The behavior of helical peptides has long been known to be well described by an Ising model treatment.…”

Section: Introductionmentioning

confidence: 99%

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Mapping the Energy Landscape of Repeat Proteins using NMR-detected Hydrogen Exchange

Cortajarena¹,

Mochrie²,

Regan³

2008

Journal of Molecular Biology

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Repeat proteins contain tandem arrays of a simple structural motif. In contrast to globular proteins, repeat proteins are stabilized only by interactions between residues that are relatively close together in the sequence, with no "long-range" interactions. Our work focuses on the tetratricopeptide repeat (TPR), a 34 amino acid helix-turn-helix motif found in tandem arrays in many natural proteins. Earlier, we reported the design and characterization of a series of consensus TPR (CTPR) proteins, which are built as arrays of multiple tandem copies of a 34 amino acid consensus sequence. Here, we present the results of extensive hydrogen exchange (HX) studies of the folding-unfolding behavior of two CTPR proteins (CTPR2 and CTPR3). We used HX to detect and characterize partially folded species that are populated at low frequency in the nominally folded state. We show that for both proteins the equilibrium folding-unfolding transition is nontwo-state, but sequential, with the outermost helices showing a significantly higher probability than inner helices of being unfolded. We show that the experimentally observed unfolding behavior is consistent with the predictions of a simple Ising model, in which individual helices are treated as "spin-equivalents". The results that we present have general implications for our understanding of the thermodynamic properties of repeat proteins.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mapping the Energy Landscape of Repeat Proteins using NMR-detected Hydrogen Exchange

Cortajarena¹,

Mochrie²,

Regan³

2008

Journal of Molecular Biology

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“…The reference and test peptides are treated by assigning an average intrinsic helix propensity, 〈w〉 host , to alanine and lysine residues. The other residues are given previously determined w and n (n-cap) values (Armstrong & Baldwin, 1993;Huyghues-Despointes et al, 1993a;Doig et al, 1994), which have been revised recently by Rohl et al (1996) …”

Section: Synthesis Of Peptides Purification and CD Measurementsmentioning

confidence: 99%

Ion-Pair and Charged Hydrogen-Bond Interactions between Histidine and Aspartate in a Peptide Helix

Huyghues-Despointes¹,

Baldwin²

1997

Biochemistry

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The effect on helix stability of placing a single pair of His-Asp or Asp-His residues, spaced (i, i + 3), (i, i + 4), or (i, i + 5), in an alanine-based peptide has been determined. The peptides have identical amino acid compositions, intrinsic helix propensities, and closely similar charge-helix dipole interactions, but they have different side chain interactions. Their helix contents are measured by circular dichroism over the pH range of 2-9, and the strength of a particular side chain interaction is determined from the increase in helix content over the reference peptide with the (i, i + 5) spacing. Side chain interactions are found for both the (i, i + 3) and (i, i + 4) spacings but only in the His-Asp orientation. Charged hydrogen-bond interactions occur at extreme pH values, and they are almost as strong as the ion-pair interactions at pH 5.5; but only the (i, i + 4) His-Asp peptide forms a strong hydrogen bond at pH 2, and only the (i, i + 3) peptide forms a strong hydrogen bond at pH 8.5. The ion-pair interactions are not screened effectively by 1 M NaCl, and hydrogen bonds probably acount for most of their strength.Whether ion-pair interactions contribute favorably to protein stability is still under discussion. Although a HisAsp salt bridge (the term salt bridge is used here to denote a H-bonded ion pair) contributes -3 to -5 kcal/mol, or about one-half of the net stability of T4 lysozyme (Anderson et al., 1990), nevertheless, attempts to increase the stability of T4 lysozyme by making engineered His-Asp ion-pair interactions were unsuccessful . Theoretical considerations suggest that the desolvation associated with burial or partial burial of charged groups should be unfavorable (Hendsch & Tidor, 1994; Honig & Nicholls, 1995) and earlier studies suggest that ion-pair interactions in proteins are strong interactions only when the interacting groups are partly buried (Friend & Gurd, 1979;Matthew & Richards, 1982;States & Karplus, 1987). Replacing three buried charged residues of Arc repressor with nonpolar residues does give increased stability [Waldburger et al., 1995; see also Hendsch et al. (1996)]. The role of ion-pair interactions in stabilizing coiled-coil dimer helices is also controversial (Krylov et al., 1994;Lumb & Kim, 1996;Lavigne et al., 1996, and references therein). The structures of some proteins from extreme thermophiles show networks of ion-pair interactions, and there is considerable curiosity about the possible role of these interactions in stabilizing proteins at high temperatures [see review in Goldman (1995)].Consequently, it is interesting to determine how effective ion-pair interactions are in stabilizing solvent-exposed peptide helices. A Glu 2-Arg 10 ion-pair interaction proved to be one of the sources of the surprising stability of the C-peptide helix from the N-terminal end of ribonuclease A [see Fairman et al. (1990) and references therein]. Repeated blocks of Glu 4 Lys 4 induce helix formation in a peptide when, in a peptide of the same amino acid composition...

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“…The charge states are often correlated to the structures, properties, and biological functions of the proteins. Studies have shown that charged groups close to the ends of helices were found to be an important determinant of the stability of the helices [2][3][4][5][6]. The extents of protonation and deprotonation are directly related to the acid-base properties of individual amino acid residues.…”

mentioning

confidence: 99%

“…Interestingly, an amino acid residue located at different positions in a folded protein often exhibits different degrees of acidity or basicity. For example, an acidic residue, such as cysteine or aspartic acid, located at or near the N-terminus of a helix is often more acidic than that at or near the C-terminus [5,[7][8][9][10][11]. A wealth of studies on the acid-base properties of helical peptides have been carried out in condensed phase, in particular in aqueous solutions [11][12][13].…”

mentioning

confidence: 99%

Gas-phase acidities of cysteine-polyglycine peptides: The effect of the cysteine position

Morishetti

Huang

Yates

et al. 2010

J. Am. Soc. Mass Spectrom.

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The sequence and conformational effects on the gas-phase acidities of peptides have been studied by using two pairs of isomeric cysteine-polyglycine peptides, CysGly 3,4 NH 2 and Gly 3,4 CysNH 2 . The extended Cooks kinetic method was employed to determine the gas-phase acidities using a triple quadrupole mass spectrometer with an electrospray ionization source. The ion activation was achieved via collision-induced dissociation experiments. The deprotonation enthalpies (⌬ acid H) were determined to be 323.9 Ϯ 2.5 kcal/mol (CysGly 3 NH 2 ), 319.2 Ϯ 2.3 kcal/mol (CysGly 4 NH 2 ), 333.8 Ϯ 2.1 kcal/mol (Gly 3 CysNH 2 ), and 321.9 Ϯ 2.8 kcal/mol (Gly 4 CysNH 2 ), respectively. The corresponding deprotonation entropies (⌬ acid S) of the peptides were estimated. The gas-phase acidities (⌬ acid G) were derived to be 318.4 Ϯ 2.5 kcal/mol (CysGly 3 NH 2 ), 314.9 Ϯ 2.3 kcal/mol (CysGly 4 NH 2 ), 327.5 Ϯ 2.1 kcal/mol (Gly 3 CysNH 2 ), and 317.4 Ϯ 2.8 kcal/mol (Gly 4 CysNH 2 ), respectively. Conformations and energetic information of the neutral and anionic peptides were calculated through simulated annealing (Tripos), geometry optimization (AM1), and single point energy calculations (B3LYP/6-31ϩG(d)), respectively. Both neutral and deprotonated peptides adopt many possible conformations of similar energies. All neutral peptides are mainly random coils. The two C-cysteine anionic peptides, Gly 3,4 (Cys-H) Ϫ NH 2 , are also random coils. The two N-cysteine anionic peptides, (Cys-H) Ϫ Gly 3,4 NH 2 , may exist in both random coils and stretched helices. The two N-cysteine peptides, CysGly 3 NH 2 and CysGly 4 NH 2 , are significantly more acidic than the corresponding C-terminal cysteine ones, Gly 3 CysNH 2 and Gly 4 CysNH 2 . The stronger acidities of the former may come from the greater stability of the thiolate anion resulting from the interaction with the helix-macrodipole, in addition to the hydrogen bonding interactions. (J Am Soc Mass Spectrom 2010, 21, 603-614)

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Effect of a single aspartate on helix stability at different positions in a neutral alanine‐based peptide

Cited by 141 publications

References 31 publications

Mapping the Energy Landscape of Repeat Proteins using NMR-detected Hydrogen Exchange

Mapping the Energy Landscape of Repeat Proteins using NMR-detected Hydrogen Exchange

Ion-Pair and Charged Hydrogen-Bond Interactions between Histidine and Aspartate in a Peptide Helix

Gas-phase acidities of cysteine-polyglycine peptides: The effect of the cysteine position

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