Polyproline II conformation is one of many local conformational states and is not an overall conformation of unfolded peptides and proteins

Makowska, Joanna; Rodziewicz‐Motowidło, Sylwia; Bagiñska, Katarzyna; Vila, Jorge A.; Liwo, Adam; Chmurzyński, Lech; Scheraga, Harold A.

doi:10.1073/pnas.0510549103

Cited by 161 publications

(229 citation statements)

References 69 publications

Supporting

Mentioning

200

Contrasting

Unclassified

Order By: Relevance

“…This noncoincidence can only be achieved with a substantive fraction of PPII-like conformations (48,56). However, our results also agree to a significant extent with Makowska et al, in that the consideration of turn-like conformations is necessary to explain our experimental results (30). We invoked the results of those authors in assuming that type IIIЈ and V turn structures predominantly involve residues 2, 3, and 4, but we would have obtained similar results if we had selected another pair of residues.…”

Section: Resultssupporting

confidence: 91%

“…For the two-state model we obtained 30 Å, which far exceeds that of 18.1 Å, derived from the radius of gyration of 7.4 Å, as obtained from SAXS data (29). In a second step, we performed a simulation that considered the entire above-mentioned conformational manifold, containing representatives of all of the local turn structures that emerged from the MD simulations of Makowska et al (30). We used the result of these simulations to initially guess the mole fractions of the respective residue conformations and subsequently varied them to optimize the simulations with respect to the measured profiles.…”

Section: Resultsmentioning

confidence: 98%

“…For residues 2 (X), 5, 6, and 9 (all Ala) we allowed type IIIЈ and type IV turns as additional conformations. This blend represents, more or less, different clusters that emerged from the MD simulations of Makowska et al (30). Their results suggest a limited sampling of conformations involving intrapeptide hydrogen bonding, hence this possibility was disregarded for the sake of simplicity.…”

Section: Resultsmentioning

confidence: 99%

“…The simulations reproduced neither the extended, PPII-dominated structure, nor the very short radius of gyration obtained from the SAXS data. Makowska et al (30) combined ECD and NMR measurements of XAO (involving the measurement of 3 J C␣HNH coupling constants, NOEs, and chemical shifts) with MD simulations performed with the AMBER 99 force field. The results led them to conclude that PPII is one of many conformations sampled by alanine.…”

mentioning

confidence: 99%

See 3 more Smart Citations

The alanine-rich XAO peptide adopts a heterogeneous population, including turn-like and polyproline II conformations

Schweitzer‐Stenner

Measey

2007

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

View full text Add to dashboard Cite

The solution structure of the hepta-alanine polypeptide Ac-X 2A7O2-NH2 (XAO) has been a matter of controversy in the current literature. On one side of the argument is a claim that the peptide adopts a mostly polyproline II ( We have used an excitonic coupling model to simulate the amide I band of the FTIR, vibrational circular dichroism, and isotropic and anisotropic Raman spectra of XAO, where, for each residue, the backbone dihedral angle was constrained by using the reported 3 JC␣HNH values and a modified Karplus relation. The best reproduction of the experimental data could only be achieved by assuming an ensemble of conformations, which contains various ␤-turn conformations (Ϸ26%), in addition to ␤-strand (Ϸ23%) and PPII (Ϸ50%) conformations. PPII is the dominant conformation in segments not involved in turn formations. Most of the residues were found to sample the bridge region connecting the PPII and right-handed helix troughs in the Ramachandran plot, which is part of the very heterogeneous ensemble of conformations generally termed type IV ␤-turn.alanine propensity ͉ amide I ͉ unfolded peptides ͉ vibrational spectroscopy T he unfolded state of peptides and proteins has been the subject of an increasing number of experimental and theoretical studies (1-9), owing to the discovery of naturally disordered, although biologically functioning, proteins and peptides (9), and the general relevance for a thorough understanding of the protein folding process. In this context, the possible existence of local residue structure would certainly affect the initial phase of the folding process (10). The existence of such locally ordered segments has first been proposed by Tiffany and Krimm (11) based on electronic circular dichroism (ECD) measurements on poly-L-proline, poly-L-lysine, and poly-L-glutamic acid. They concluded that charged polypeptides assume, at least locally, a rather ordered polyproline II (PPII) conformation, which is the structure adopted by trans-poly-L-proline. This notion was later confirmed by vibrational circular dichroism (VCD) studies on a variety of unfolded polypeptides and proteins (12,13).PPII is a rather regular structural motif in that it exhibits a perfect, left-handed threefold rotational symmetry (3 1 -helix) for its canonical conformation, with ( , ) ϭ (Ϫ78°, 146°) (14). Woody and coworkers (15-17) have published a series of papers proving that PPII gives rise to a far UV-ECD spectrum, which many in the scientific community still interpret as indicative of random coil (15). Recently, they reported a very convincing quantitative agreement between the PPII content of ␤II proteins, derived from crystallographic data, and ECD spectra (16). The PPII signal was also observed in the spectrum of the unfolded state of many proteins subjected to denaturing detergents (17). Thermal denaturation, however, often yields a conformation that is reflected by a weak, nearly symmetric, couplet with a positive maximum between 180 and 210 nm and a negative minimum between 210 and 230 nm (11,16,18). ECD ...

show abstract

Section: Resultssupporting

confidence: 91%

Section: Resultsmentioning

confidence: 98%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

The alanine-rich XAO peptide adopts a heterogeneous population, including turn-like and polyproline II conformations

Schweitzer‐Stenner

Measey

2007

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

View full text Add to dashboard Cite

show abstract

“…This peptide is too short to form a stable ␣-helix and therefore should be a random coil. Contrary to this expectation, the peptide is largely in P II conformation, in agreement with predictions from theory (73), although the issue is not without controversy (74). Loss of conformational entropy on folding.…”

Section: What Anfinsen Could Not Have Knownsupporting

confidence: 76%

A backbone-based theory of protein folding

Rose

Fleming

Banavar

et al. 2006

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

448

412

View full text Add to dashboard Cite

Under physiological conditions, a protein undergoes a spontaneous disorder º order transition called "folding." The protein polymer is highly flexible when unfolded but adopts its unique native, three-dimensional structure when folded. Current experimental knowledge comes primarily from thermodynamic measurements in solution or the structures of individual molecules, elucidated by either x-ray crystallography or NMR spectroscopy. From the former, we know the enthalpy, entropy, and free energy differences between the folded and unfolded forms of hundreds of proteins under a variety of solvent͞cosolvent conditions. From the latter, we know the structures of Ϸ35,000 proteins, which are built on scaffolds of hydrogen-bonded structural elements, ␣-helix and ␤-sheet. Anfinsen showed that the amino acid sequence alone is sufficient to determine a protein's structure, but the molecular mechanism responsible for self-assembly remains an open question, probably the most fundamental open question in biochemistry. This perspective is a hybrid: partly review, partly proposal. First, we summarize key ideas regarding protein folding developed over the past half-century and culminating in the current mindset. In this view, the energetics of side-chain interactions dominate the folding process, driving the chain to self-organize under folding conditions. Next, having taken stock, we propose an alternative model that inverts the prevailing side-chain͞backbone paradigm. Here, the energetics of backbone hydrogen bonds dominate the folding process, with preorganization in the unfolded state. Then, under folding conditions, the resultant fold is selected from a limited repertoire of structural possibilities, each corresponding to a distinct hydrogen-bonded arrangement of ␣-helices and͞or strands of ␤-sheet.

show abstract

The Structure of Unfolded Peptides and Proteins Explored by Vibrational Spectroscopy

Schweitzer‐Stenner¹,

Measey²,

Hagarman³

et al. 2010

Instrumental Analysis of Intrinsically Disordered Proteins

View full text Add to dashboard Cite

7The exploration of unfolded peptides and proteins is an emerging area of research in the fi eld of protein biophysics and biochemistry. In this context, vibrational spectroscopy has become a valuable tool for exploring local structural preferences of amino acid residues in the unfolded state. After introducing the basic physical concepts, this article reviews the most recent utilization of UV resonance Raman, visible nonresonance Raman, vibrational circular dichroism, Raman optical activity, and, to a limited extent, electronic circular dichroism spectroscopy for the exploration of naturally unfolded peptides and proteins. With respect to peptides, this article puts an emphasis on recent work about alanine -based peptides, which, owing to the large abundance of alanine in proteins, have emerged as ideal model systems for attempts to understand structure and dynamics in the unfolded state. ABSTRACT 3 3 3 J J J

show abstract

Polyproline II conformation is one of many local conformational states and is not an overall conformation of unfolded peptides and proteins

Cited by 161 publications

References 69 publications

The alanine-rich XAO peptide adopts a heterogeneous population, including turn-like and polyproline II conformations

The alanine-rich XAO peptide adopts a heterogeneous population, including turn-like and polyproline II conformations

A backbone-based theory of protein folding

The Structure of Unfolded Peptides and Proteins Explored by Vibrational Spectroscopy

Contact Info

Product

Resources

About