A single carboxy-terminal arginine determines the amino-terminal helix conformation of an alanine-based peptide

Fiori, Wayne R.; Lundberg, Karen M.; Millhauser, Glenn L.

doi:10.1038/nsb0694-374

Cited by 42 publications

(51 citation statements)

References 38 publications

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“…28 The termini were capped to remove potentially destabilizing electrostatic interactions with the helix dipole. 29 This was accomplished by acetylation of the N-terminus with acetic anhydride and the use of MBHA Rink Amide resin to amidate the C-terminus.…”

Section: Methodsmentioning

confidence: 99%

The effect of mutations on peptide models of the DNA binding helix of p53: Evidence for a correlation between structure and tumorigenesis

Trulson¹,

Millhauser²

1999

Biopolymers

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Section: Methodsmentioning

confidence: 99%

The effect of mutations on peptide models of the DNA binding helix of p53: Evidence for a correlation between structure and tumorigenesis

Trulson¹,

Millhauser²

1999

Biopolymers

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“…It should be noted that from the NOEs observed, the calculated structure may reflect a time averaged conformation for the peptide undergoing a dynamic transition between, for example, ␣-and 3 10 -helix (e.g., Refs. [33][34][35]. Towards the C terminus of the peptide (residues 21-25), the regular pattern of ␣-helical NOEs is resumed with the calculated structure adopting that of a regular ␣-helix.…”

mentioning

confidence: 99%

Determination of the Structure of the N-terminal Splice Region of the Cyclic AMP-specific Phosphodiesterase RD1 (RNPDE4A1) by 1H NMR and Identification of the Membrane Association Domain Using Chimeric Constructs

Smith

Scotland

Beattie

et al. 1996

Journal of Biological Chemistry

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A 25-residue peptide representing the membrane targeting N-terminal splice region of the cyclic AMP phosphodiesterase RD1 (RNPDE4A1) was synthesized, and its structure was determined by 1 H NMR. Two independently folding helical regions were identified, separated by a highly mobile "hinge" region. The first helical region was formed by an N-terminal amphipathic ␣-helix, and the second consisted of multiple overlapping turns and contained a distinct compact, hydrophobic, tryptophan-rich domain (residues 14 -20). Chimeric molecules, formed between the N-terminal region of RD1 and the soluble bacterial protein chloramphenicol acetyltransferase, were used in an in vitro system to determine the features within the splice region that were required for membrane association. The ability of RD1-chloramphenicol acetyltransferase chimera to become membrane-associated was not affected by deletion of any of the following regions: the apolar section (residues 2-7) of the first helical region, the polar part of this region together with the hinge region (residues 8 -13), or the polar end of the C-terminal helical region (residues 21-25). In marked contrast, deletion of the compact, hydrophobic tryptophan-rich domain (residues 14 -20) found in the second helical region obliterated membrane association. Replacement of this domain with a hydrophobic cassette of seven alanine residues also abolished membrane association, indicating that membrane-association occurred by virtue of specific hydrophobic interactions with residues within the compact, tryptophan-rich domain. The structure of this domain is well defined in the peptide, and although the region is helical, both the backbone and the distribution of side chains are somewhat distorted as compared with an ideal ␣-helix. Hydrophobic interactions, such as the "stacked" rings of residues Pro 14 and Trp 15 , stabilize this domain with the side chain of residue Leu 16 adopting a central position, interacting with the side chains of all three tryptophan residues 15, 19, and 20. These bulky side chains thus form a hydrophobic cluster. In contrast, the side chain of residue Val 17 is relatively exposed, pointing out from the opposite "face" of the peptide. Although it appears that this compact, tryptophan-rich domain is responsible for membrane association, at present the target site and hence the specific interactions involved in membrane targeting by the RD1 splice region remain unidentified.

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“…It has been proposed that peptides made of the standard 20 L-amino acids can form 3,0-helices (Miick et al, 1992), or at least populate a significant amount of 3,,-helix at their N-and C-termini. The fraction of 3,,-helix present in a helical peptide is certainly strongly sequence dependent (Fiori et al, 1994;Zhou et al, 1994). 3,,-Helix formation can be induced by the introduction of a c,,,-disubstituted a-amino acid, of which a-aminoisobutyric acid (AIB) is the prototype.…”

Section: Introductionmentioning

confidence: 99%

Models for the 3₁₀‐helix/coil, π‐helix/coil, and α‐helix/3₁₀‐helix/coil transitions in isolated peptides

Rohl

Doig

1996

Protein Science

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Models for the 310-helix/coil and a-helix/coil equilibria have been derived. The theory is based on classifying residues into helical or nonhelical (coil) conformations. Statistical weights are assigned to residues in a helical conformation with an associated helical hydrogen bond, a helical conformation with no hydrogen bond, an N-cap position, a C-cap position, or the reference coil conformation. The models for a-helix formation and 3,,-helix formation have also been combined to describe a three-state equilibrium in which a-helical, 3,,-helical, and coil conformations are populated. The results are compared with the modified Lifson-Roig theory for the a-helix/coil equilibrium. The comparison accounts for the experimental observations that 310-helices tend to be short and a-helices are not favored for any length. This work may provide a framework for quantitatively rationalizing experimental work on isolated 310-helices and mixed 310-/a-helices.Keywords: a-helix; helix-coil transition theory; N-cap; a-helix; 3,,-helix Polypeptide helices are stabilized by periodic hydrogen bonds between backbone CO and NH groups. They can be described by the number of residues per helical turn and the number of atoms contained in the ring made by each hydrogen bond (Bragg et al., 1950). The ideal a-helix has a periodicity of 3.6 residues per turn, encloses 13 atoms in a ring by formation of an i , i + 4 C=O.. .H-N hydrogen bond and is thus a 3.6,,-helix.The 3,,-helix is a more tightly wound helix, stabilized by i, i + 3 C=O. . .H-N hydrogen bonds, whereas the s-(4.4,,-)helix is wound less tightly with i, i + 5 C=O. . .H-N hydrogen bonds.The 3,,-helix was proposed and discussed (Huggins, 1943; Bragg et al., 1950;Donohue, 1953) earlier than the a-helix (Pauling et al., 1951). Although appreciably less common than a-helices, 3-4'70 of residues in crystal structures are in 3,,-helices (Barlow & Thornton, 1988; Karpen et al., 1992), making the 3,,-helix the fourth most common type of secondary structure in proteins after a-helices, @-sheets, and reverse turns. Most 3,,-helices are short, only three or four residues long, compared with a mean of ten residues in a-helices (Barlow & Thornton, 1988 Hubbard, 1984;Barlow & Thornton, 1988): 32% of helices in crystal structures were found to have a 3,,-type hydrogen bond at their N-termini and 34% at their C-termini (Baker & Hubbard, 1984). Strong amino acid preferences have been observed for different locations within a 3,,-helix in a recent survey of crystal structures (Karpen et al., 1992).3,,-Helices have also been studied in isolated peptides. It has been proposed that peptides made of the standard 20 L-amino acids can form 3,0-helices (Miick et al., 1992), or at least populate a significant amount of 3,,-helix at their N-and C-termini. The fraction of 3,,-helix present in a helical peptide is certainly strongly sequence dependent (Fiori et al., 1994;Zhou et al., 1994). 3,,-Helix formation can be induced by the introduction of a c,,,-disubstituted a-amino acid, of which a-ami...

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A single carboxy-terminal arginine determines the amino-terminal helix conformation of an alanine-based peptide

Cited by 42 publications

References 38 publications

The effect of mutations on peptide models of the DNA binding helix of p53: Evidence for a correlation between structure and tumorigenesis

The effect of mutations on peptide models of the DNA binding helix of p53: Evidence for a correlation between structure and tumorigenesis

Determination of the Structure of the N-terminal Splice Region of the Cyclic AMP-specific Phosphodiesterase RD1 (RNPDE4A1) by 1H NMR and Identification of the Membrane Association Domain Using Chimeric Constructs

Models for the 3₁₀‐helix/coil, π‐helix/coil, and α‐helix/3₁₀‐helix/coil transitions in isolated peptides

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A single carboxy-terminal arginine determines the amino-terminal helix conformation of an alanine-based peptide

Cited by 42 publications

References 38 publications

The effect of mutations on peptide models of the DNA binding helix of p53: Evidence for a correlation between structure and tumorigenesis

The effect of mutations on peptide models of the DNA binding helix of p53: Evidence for a correlation between structure and tumorigenesis

Determination of the Structure of the N-terminal Splice Region of the Cyclic AMP-specific Phosphodiesterase RD1 (RNPDE4A1) by 1H NMR and Identification of the Membrane Association Domain Using Chimeric Constructs

Models for the 310‐helix/coil, π‐helix/coil, and α‐helix/310‐helix/coil transitions in isolated peptides

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Models for the 3₁₀‐helix/coil, π‐helix/coil, and α‐helix/3₁₀‐helix/coil transitions in isolated peptides