Fast events in protein folding: Relaxation dynamics of secondary and tertiary structure in native apomyoglobin

Gilmanshin, Rudolf; Williams, Sharon; Callender, Robert; Woodruff, William H.; Dyer, R. Brian

doi:10.1073/pnas.94.8.3709

Cited by 222 publications

(251 citation statements)

References 31 publications

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“…The more traditional picture of protein dynamics starts from the assumption of a continuum of time scales, leading to a nonexponential but monotonic decay, which commonly is modeled by stretched exponentials or power laws (23,(41)(42)(43)(44). The latter response is frequently observed in much larger systems, in particular at low temperatures, and emphasizes the glass-like behavior of proteins (1)(2)(3)(4)(5)(6)(7). In view of the small size of the peptide studied here, its complex response seems surprising.…”

Section: Discussionmentioning

confidence: 99%

“…Albeit possessing only a few conformational degrees of freedom compared with a protein, the peptide behaves highly nontrivially and provides insights into the complexity of fast protein folding. P rotein dynamics occurs on a large range of time scales, which can coarsely be related to various length scales of proteins: dynamics of tertiary and quaternary structure extends from milliseconds to seconds and even longer, whereas formation of secondary structure has been observed between 50 ns and a few microseconds (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11). Nevertheless, several experiments have provided strong hints for the relevance of even faster processes from the observation of large instantaneous signals, which could not be time resolved (2,7,12).…”

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confidence: 99%

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Picosecond conformational transition and equilibration of a cyclic peptide

Bredenbeck

Helbing

Sieg

et al. 2003

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

163

196

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Ultrafast IR spectroscopy is used to monitor the nonequilibrium backbone dynamics of a cyclic peptide in the amide I vibrational range with picosecond time resolution. A conformational change is induced by means of a photoswitch integrated into the peptide backbone. Although the main conformational change of the backbone is completed after only 20 ps, the subsequent equilibration in the new region of conformational space continues for times >16 ns. Relaxation and equilibration processes of the peptide backbone occur on a discrete hierarchy of time scales. Albeit possessing only a few conformational degrees of freedom compared with a protein, the peptide behaves highly nontrivially and provides insights into the complexity of fast protein folding.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Picosecond conformational transition and equilibration of a cyclic peptide

Bredenbeck

Helbing

Sieg

et al. 2003

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

163

196

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“…The first steps involve a and b globin gene translation, which takes place on the order of a few minutes per subunit (25,51,63,72,73). Given that a helices and other structural features are capable of forming spontaneously in less than a few microseconds (30,36,41,111), it is plausible that a and b chains could acquire some of their secondary and tertiary structure co-translationally. Several studies using cell-free protein expression systems support this idea and suggest that heme or hemin insertion is also a co-translational process (65,66,95).…”

Section: Pathways For Hemoglobin Assembly In Vivo and In Vitromentioning

confidence: 99%

The Role of Alpha-Hemoglobin Stabilizing Protein in Redox Chemistry, Denaturation, and Hemoglobin Assembly

Mollan

Weiss

et al. 2010

Antioxidants & Redox Signaling

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Hemoglobin biosynthesis in erythrocyte precursors involves several steps. The correct ratios and concentrations of normal alpha (a) and beta (b) globin proteins must be expressed; apoproteins must be folded correctly; heme must be synthesized and incorporated into these globins rapidly; and the individual a and b subunits must be rapidly and correctly assembled into heterotetramers. These events occur on a large scale in vivo, and dysregulation causes serious clinical disorders such as thalassemia syndromes. Recent work has implicated a conserved erythroid protein known as Alpha-Hemoglobin Stabilizing Protein (AHSP) as a participant in these events. Current evidence suggests that AHSP enhances a subunit stability and diminishes its participation in harmful redox chemistry. There is also evidence that AHSP facilitates one or more early-stage post-translational hemoglobin biosynthetic events. In this review, recent experimental results are discussed in light of several current models describing globin subunit folding, heme uptake, assembly, and denaturation during hemoglobin synthesis. Particular attention is devoted to molecular interactions with AHSP that relate to a chain oxidation and the ability of a chains to associate with partner b chains. Antioxid. Redox Signal. 12, 219-232.

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“…IR spectroscopy on amide I transitions (primarily CO stretching; 1,600-1,700 cm Ϫ1 ) has been widely used for folding studies of proteins (7,(14)(15)(16)(17) and peptides (9,(18)(19)(20), primarily because amide I spectra have peak positions that depend on secondary structure. The frequency-structure correlation is a result of through-space electrostatic couplings that depend on the distance and orientation between the many amide I vibrations of each of the protein's peptide units (21,22).…”

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confidence: 99%

Conformational changes during the nanosecond-to-millisecond unfolding of ubiquitin

Chung

Khalil

Smith

et al. 2005

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

157

187

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Steady-state and transient conformational changes upon the thermal unfolding of ubiquitin were investigated with nonlinear IR spectroscopy of the amide I vibrations. Equilibrium temperaturedependent 2D IR spectroscopy reveals the unfolding of the ␤-sheet of ubiquitin through the loss of cross peaks formed between transitions arising from delocalized vibrations of the ␤-sheet. Transient unfolding after a nanosecond temperature jump is monitored with dispersed vibrational echo spectroscopy, a projection of the 2D IR spectrum. Whereas the equilibrium study follows a simple two-state unfolding, the transient experiments observe complex relaxation behavior that differs for various spectral components and spans 6 decades in time. The transient behavior can be separated into fast and slow time scales. From 100 ns to 0.5 ms, the spectral features associated with ␤-sheet unfolding relax in a sequential, nonexponential manner, with time constants of 3 s and 80 s. By modeling the amide I vibrations of ubiquitin, this observation is explained as unfolding of the less stable strands III-V of the ␤-sheet before unfolding of the hairpin that forms part of the hydrophobic core. This downhill unfolding is followed by exponential barrier-crossing kinetics on a 3-ms time scale.protein-folding dynamics ͉ temperature jump ͉ nonlinear IR spectroscopy D escribing the conformational changes of proteins as they fold from a disordered denatured state to a compact native state remains an important experimental objective. Studies that examine this subject provide a molecular interpretation to the conceptual framework of the energy landscape picture (1-3) and allow more direct comparison of experiment and simulation (4, 5). Viewed as a problem in molecular dynamics, characterizing protein folding poses considerable challenges because it calls for a statistical yet structurally sensitive description of a heterogeneous ensemble in solution evolving over many decades in time.Most protein-folding experiments measure kinetics: the rate of appearance or disappearance of an experimental signature for a particular species, typically on millisecond or longer time scales. These results give information on the height of energetic barriers much higher than thermal energy but say little about how structure changed along the path. A number of fast folding experiments of proteins and peptides have shown that downhill folding, in which evolution is governed by energy barriers ՇkT, can be initiated with a nanosecond temperature jump (T-jump). Such experiments work in a diffusive regime that allows a freer exploration of available structures and provide evidence that the relevant molecular time scales for folding is nanoseconds to microseconds (6-9). If downhill folding can be initiated and followed with a structure-sensitive probe, then meaningful information can be obtained on the underlying molecular dynamics of folding. We report here on such an experiment, a conformationally sensitive probing of downhill unfolding of ubiquitin over nanosecond-to-millise...

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Fast events in protein folding: Relaxation dynamics of secondary and tertiary structure in native apomyoglobin

Cited by 222 publications

References 31 publications

Picosecond conformational transition and equilibration of a cyclic peptide

Picosecond conformational transition and equilibration of a cyclic peptide

The Role of Alpha-Hemoglobin Stabilizing Protein in Redox Chemistry, Denaturation, and Hemoglobin Assembly

Conformational changes during the nanosecond-to-millisecond unfolding of ubiquitin

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