Conservation of Protein Structure over Four Billion Years

Inglés-Prieto, Álvaro; Ibarra‐Molero, Beatriz; Delgado-Delgado, Asunción; Pérez-Jiménez, Raúl; Fernández, Julio M.; Gaucher, Eric A.; Sanchez-Ruiz, José M.; Gavira, José A.

doi:10.1016/j.str.2013.06.020

Cited by 134 publications

(148 citation statements)

References 46 publications

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“…To answer this question, we turned our attention to the analysis of the thermodynamics and kinetics of the Trx proteins for which sequences were obtained from ASR (41,55). ASR is a bioinformatics technique that allows sequence extrapolation from extant protein sequences back to their common ancestors.…”

Section: Resultsmentioning

confidence: 99%

“…These sequences were dated back to over 4 billion years, thus enabling us to probe the thermodynamics and kinetics of folding/ unfolding for proteins with sequences that arguably represent a wide evolutionary timespan (41). Furthermore, the crystal structures of these proteins have been determined and support the high conservation of the Trx protein fold (55).…”

Section: Resultsmentioning

confidence: 99%

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Evidence for the principle of minimal frustration in the evolution of protein folding landscapes

Tzul

Vasilchuk

Makhatadze

2017

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

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Theoretical and experimental studies have firmly established that protein folding can be described by a funneled energy landscape. This funneled energy landscape is the result of foldable protein sequences evolving following the principle of minimal frustration, which allows proteins to rapidly fold to their native biologically functional conformations. For a protein family with a given functional fold, the principle of minimal frustration suggests that, independent of sequence, all proteins within this family should fold with similar rates. However, depending on the optimal living temperature of the organism, proteins also need to modulate their thermodynamic stability. Consequently, the difference in thermodynamic stability should be primarily caused by differences in the unfolding rates. To test this hypothesis experimentally, we performed comprehensive thermodynamic and kinetic analyses of 15 different proteins from the thioredoxin family. Eight of these thioredoxins were extant proteins from psychrophilic, mesophilic, or thermophilic organisms. The other seven protein sequences were obtained using ancestral sequence reconstruction and can be dated back over 4 billion years. We found that all studied proteins fold with very similar rates but unfold with rates that differ up to three orders of magnitude. The unfolding rates correlate well with the thermodynamic stability of the proteins. Moreover, proteins that unfold slower are more resistant to proteolysis. These results provide direct experimental support to the principle of minimal frustration hypothesis.protein folding | protein stability | protein evolution T he energy landscape theory provides a conceptual physicochemical framework for understanding protein folding. This theory is based on the principle of minimal frustration that ". . .quantifies the dominance of interactions stabilizing the specific native structure over other interactions that would favor nonnative, topologically distinct traps" (1). A consequence of this is that the folding energy landscape of naturally occurring proteins is funnel-shaped (1-22). The shape of this funnel depends on two main factors that can introduce frustration and roughness: topology and the extent of nonnative interactions. Topological frustration can occur when certain native interactions are formed too early and need to be undone to allow for other interactions to form first, leading to backtracking and/or cracking (23-28). Weak nonnative interactions can have complex effects on the folding landscape (29-31): small amounts of weak nonnative interactions can assist folding, whereas larger amounts can create internal friction that will slow folding (32-35). For a given protein fold, both topological and energetic frustrations will depend on the amino acid sequence. Theoretical studies have suggested that naturally occurring proteins have selected sequences that are compatible with the principle of minimal frustration (36).The goal of this study is to experimentally test the evolutionary validity of the principle...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Evidence for the principle of minimal frustration in the evolution of protein folding landscapes

Tzul

Vasilchuk

Makhatadze

2017

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

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“…The authors interpret this result as evidence of the principle of minimal frustration. Their study includes several resurrected Precambrian thioredoxins that we have previously prepared and characterized (2)(3)(4)(5).…”

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confidence: 99%

Fast folding and slow unfolding of a resurrected Precambrian protein

Candel

Romero-Romero

Gamiz-Arco

et al. 2017

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

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“…These ancestral sequences were deduced by means of MrBayes (Ronquist and Huelsenbeck, 2003) and a simple F81-like model (Felsenstein, 1981). Frequently, the functions CODEML and ML of PAML (Yang, 1997) were utilized (Yokoyama and Radlwimmer, 2001;Bridgham et al, 2006;Gaucher et al, 2008;Yokoyama et al, 2008;Perez-Jimenez et al, 2011;Hobbs et al, 2012;Akanuma et al, 2013;Ingles-Prieto et al, 2013) in combination with gamma distributions modeling variable replacement rates across sites. However, different substitution matrices were chosen: in some cases the JTT model (Jones et al, 1992) was the basis for a marginal reconstruction and the synthesis of ancestral enzymes (Voordeckers et al, 2012), the same model was used in (Eick et al, 2012) in combination with the Lazarus software (Hanson-Smith et al, 2010).…”

Section: Current Software Protocols For Asrmentioning

confidence: 99%

“…Along these lines, billions-of-years old Precambrian proteins have been resurrected (Gaucher et al, 2008;Perez-Jimenez et al, 2011;Akanuma et al, 2013;Ingles-Prieto et al, 2013;Risso et al, 2013;Reisinger et al, 2014;Risso et al, 2014). As a side-effect, these studies allow one to obtain information about environmental conditions surrounding Precambrian life.…”

Section: Applications Of Asr Deducing Environmental Conditions Of Thementioning

confidence: 99%

Ancestral protein reconstruction: techniques and applications

Merkl

Sterner

2016

Biological Chemistry

134

104

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Ancestral sequence reconstruction (ASR) is the calculation of ancient protein sequences on the basis of extant ones. It is most powerful in combination with the experimental characterization of the corresponding proteins. Such analyses allow for the study of problems that are otherwise intractable. For example, ASR has been used to characterize ancestral enzymes dating back to the Paleoarchean era and to deduce properties of the corresponding habitats. In addition, the historical approach underlying ASR enables the identification of amino acid residues key to protein function, which is often not possible by only comparing extant proteins. Along these lines, residues responsible for the spectroscopic properties of protein pigments were identified as well as residues determining the binding specificity of steroid receptors. Further applications are studies related to the longevity of mutations, the contribution of gene duplications to enzyme functionalization, and the evolution of protein complexes. For these applications of ASR, we discuss recent examples; moreover, we introduce the basic principles of the underlying algorithms and present state-of-the-art protocols.

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Conservation of Protein Structure over Four Billion Years

Cited by 134 publications

References 46 publications

Evidence for the principle of minimal frustration in the evolution of protein folding landscapes

Evidence for the principle of minimal frustration in the evolution of protein folding landscapes

Fast folding and slow unfolding of a resurrected Precambrian protein

Ancestral protein reconstruction: techniques and applications

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