How strong are side chain interactions in the folding intermediate?

Samatova, Ekaterina; Katina, N. S.; Balobanov, Vitaly A.; Melnik, Bogdan S.; Долгих, Д. А.; Bychkova, Valentina E.; Finkelstein, Alan

doi:10.1002/pro.229

Cited by 22 publications

(35 citation statements)

References 48 publications

(40 reference statements)

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“…Similarly Dobson (Lindorff-Larsen et al 2004 argues that a small network of hydrophobic contacts defines the native topology in the TSE. Further evidence that the requirement for a nucleus, which involves NLIs and directs the formation of the TSE, is a general feature of the folding mechanism was described by many researchers (Fulton et al 1999;Paci et al 2003;Geierhaas et al 2004;Krantz et al 2004;Sosnick et al 2004;Lappalainen et al 2008;Tsong et al 2008;Samatova et al 2009). …”

Section: O'neill Et Al (O'neill and Robert Matthews 2000)mentioning

confidence: 79%

The loop hypothesis: contribution of early formed specific non-local interactions to the determination of protein folding pathways

et al. 2013

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The extremely fast and efficient folding transition (in seconds) of globular proteins led to the search for some unifying principles embedded in the physics of the folding polypeptides. Most of the proposed mechanisms highlight the role of local interactions that stabilize secondary structure elements or a folding nucleus as the starting point of the folding pathways, i.e., a "bottom-up" mechanism. Nonlocal interactions were assumed either to stabilize the nucleus or lead to the later steps of coalescence of the secondary structure elements. An alternative mechanism was proposed, an "up-down" mechanism in which it was assumed that folding starts with the formation of very few non-local interactions which form closed long loops at the initiation of folding. The possible biological advantage of this mechanism, the "loop hypothesis", is that the hydrophobic collapse is associated with ordered compactization which reduces the chance for degradation and misfolding. In the present review the experiments, simulations and theoretical consideration that either directly or indirectly support this mechanism are summarized. It is argued that experiments monitoring the time-dependent development of the formation of specifically targeted early-formed sub-domain structural elements, either long loops or secondary structure elements, are necessary. This can be achieved by the timeresolved FRET-based "double kinetics" method in combination with mutational studies. Yet, attempts to improve the time resolution of the folding initiation should be extended down to the sub-microsecond time regime in order to design experiments that would resolve the classes of proteins which first fold by local or non-local interactions.

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Section: O'neill Et Al (O'neill and Robert Matthews 2000)mentioning

confidence: 79%

The loop hypothesis: contribution of early formed specific non-local interactions to the determination of protein folding pathways

et al. 2013

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“…In the Laboratory of Protein Physics (Institute of Protein Research, Russian Academy of Sciences) a detailed study of apoMb folding was done. The object of the investigation was the kinetics of folding of mutant proteins with substitutions both in the conserved and non conserved positions important for folding [52,53].…”

Section: Conformational State Of Globular Proteins In the Presence Ofmentioning

confidence: 99%

How membrane surface affects protein structure

Bychkova

Basova

Balobanov

2014

Biochemistry Moscow

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The immediate environment of the negatively charged membrane surface is characterized by decreased dielectric constant and pH value. These conditions can be modeled by water-alcohol mixtures at moderately low pH. Several globular proteins were investigated under these conditions, and their conformational behavior in the presence of phospholipid membranes was determined, as well as under conditions modeling the immediate environment of the membrane surface. These proteins underwent conformational transitions from the native to a molten globule-like state. Increased flexibility of the protein structure facilitated protein functioning. Our experimental data allow understanding forces that affect the structure of a protein functioning near the membrane surface (in other words, in the membrane field). Similar conformational states are widely reported in the literature. This indicates that the negatively charged membrane surface can serve as a moderately denaturing agent in the cell. We conclude that the effect of the membrane field on the protein structure must be taken into account.

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“…Numerous works showed that local and non-local contact are critical for the proper folding in both hierarchical and nucleation-condensation folding models. Studies of various mutants of apomyoglobin of different sources were reported by several groups where contributions of both local and non-local interactions were found [33,[76][77][78][79][80]. Numerous studies of the folding of SH3 domains showed a similar sequence of events where non-local contacts lead to the formation of a nucleus [23][24][25][81][82][83][84][85], and the context dependence of secondary structure formation was also shown [86].…”

Section: The Interplay Of Local and Non-local Interactions In The Folmentioning

confidence: 99%

“…Furthermore, they proposed that protein folding occurs through consecutive looping of the chain, with the loops ending primarily at hydrophobic nuclei. The role of non-local interactions in the early phases of folding pathways was described in many studies [23][24][25][26][27][28][29][30][31][32][33][34].…”

Section: Introductionmentioning

confidence: 99%

Fast closure of long loops at the initiation of the folding transition of globular proteins studied by time-resolved FRET-based methods

Orevi

Rahamim

Shemesh

et al. 2014

Bio-Algorithms and Med-Systems

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The protein folding problem would be considered "solved" when it will be possible to "read genes", i.e., to predict the native fold of proteins, their dynamics, and the mechanism of fast folding based solely on sequence data. The long-term goal should be the creation of an algorithm that would simulate the stepwise mechanism of folding, which constrains the conformational space and in which random search for stable interactions is possible. Here, we focus attention on the initial phases of the folding transition starting with the compact disordered collapsed ensemble, in search of the initial sub-domain structural biases that direct the otherwise stochastic dynamics of the backbone. Our studies are designed to test the "loop hypothesis", which suggests that fast closure of long loop structures by non-local interactions between clusters of mainly non-polar residues is an essential conformational step at the initiation of the folding transition of globular proteins. We developed and applied experimental methods based on time-resolved resonance excitation energy transfer (trFRET) measurements combined with fast mixing methods and studied the initial phases of the folding of Escherichia coli adenylate kinase (AK). A series of AK mutants were prepared, in which the ends of selected backbone segments that form long closed loops or secondary structure elements were labeled by donors and acceptors of excitation energy. The end-to-end distance distributions of such segments were determined under equilibrium and during the fast folding transitions. These experiments show that three out of seven long loops that were labeled in the AK molecule are closed very early in the transition. The N terminal 26-residue loop (loop I) is closed in < 200 μs after the initiation of folding, while the β strand included in loop I is still disordered. The closure of the second 44-residue loop (loop II, which starts at the end of loop I) is also complete within < 300 μs. Four other loops as well as five secondary structures of the CORE domain of AK (an α helix and four β strands) are formed at a late step, at a rate of 0.5 ± 0.3 s -1 , the rate of the cooperative folding of the molecule. These experiments reveal a hierarchically ordered pathway of folding of the AK molecule, ranging from microseconds to seconds. The results reviewed here, obtained mainly from studying a small number of model proteins, support the counterintuitive mechanism whereby non-local interactions are effective in the initiation of the folding pathways. The experiments presented demonstrate the importance of mapping the rates of sub-domain structural transitions along the folding transition, in situ, in the context of the other sections of the chain, whether folded or disordered. These experiments also show the power of the time-resolved FRET measurements in achieving this goal. A large body of data obtained by theoretical and experimental studies that support, or can accommodate, the loop hypothesis is reviewed. We suggest that mapping multiple sub-domain structural tr...

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How strong are side chain interactions in the folding intermediate?

Cited by 22 publications

References 48 publications

The loop hypothesis: contribution of early formed specific non-local interactions to the determination of protein folding pathways

The loop hypothesis: contribution of early formed specific non-local interactions to the determination of protein folding pathways

How membrane surface affects protein structure

Fast closure of long loops at the initiation of the folding transition of globular proteins studied by time-resolved FRET-based methods

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