Protein Conformational Diversity Correlates with Evolutionary Rate

Zea, Diego Javier; Monzón, Alexander Miguel; Fornasari, Marı́a Silvina; Marino-Buslje, Cristina; Parisi, Gustavo

doi:10.1093/molbev/mst065

Cited by 34 publications

(16 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In particular, a much stronger determinant of evolutionary rate seems to be expression level , which may arise from selection against misfolding during translation and avoidance of promiscuous interactions . In addition, correspondences have been observed between an increased overall rate of evolution and both increased contact density and decreased conformational diversity at the global protein level. Thus, it is not correct to say that more flexible proteins are generally less conserved – the relationship is primarily observed at the local level of residues within individual proteins.…”

Section: Local Structural Constraints Control Both Local Residue Flexmentioning

confidence: 99%

Parallel dynamics and evolution: Protein conformational fluctuations and assembly reflect evolutionary changes in sequence and structure

Marsh

Teichmann

2013

BioEssays

View full text Add to dashboard Cite

Protein structure is dynamic: the intrinsic flexibility of polypeptides facilitates a range of conformational fluctuations, and individual protein chains can assemble into complexes. Proteins are also dynamic in evolution: significant variations in secondary, tertiary and quaternary structure can be observed among divergent members of a protein family. Recent work has highlighted intriguing similarities between these structural and evolutionary dynamics occurring at various levels. Here we review evidence showing how evolutionary changes in protein sequence and structure are often closely related to local protein flexibility and disorder, large-scale motions and quaternary structure assembly. We suggest that these correspondences can be largely explained by neutral evolution, while deviations between structural and evolutionary dynamics can provide valuable functional insights. Finally, we address future prospects for the field and practical applications that arise from a deeper understanding of the intimate relationship between protein structure, dynamics, function and evolution.

show abstract

Section: Local Structural Constraints Control Both Local Residue Flexmentioning

confidence: 99%

Parallel dynamics and evolution: Protein conformational fluctuations and assembly reflect evolutionary changes in sequence and structure

Marsh

Teichmann

2013

BioEssays

View full text Add to dashboard Cite

show abstract

“…). Conformational diversity is a key concept to understand many processes and mechanisms in protein function, such as enzyme catalysis, promiscuity in protein interactions, protein‐protein recognition, signal transduction, mechanisms of disease‐related mutations, immune escape, the origin of neurodegenerative diseases, protein evolutionary rates, conformer‐specific substitution patterns, the origins of new biological functions, molecular motors, and co‐evolutionary measurements between residues (for a recent review please see). Furthermore, we have recently shown that the distribution of CD in a large dataset of proteins, with experimentally determined CD (approximately 5000 proteins), results in three main groups of proteins with different structure‐function relationships .…”

Section: Discussionmentioning

confidence: 99%

Homology modeling in a dynamical world

et al. 2017

Self Cite

View full text Add to dashboard Cite

A key concept in template-based modeling (TBM) is the high correlation between sequence and structural divergence, with the practical consequence that homologous proteins that are similar at the sequence level will also be similar at the structural level. However, conformational diversity of the native state will reduce the correlation between structural and sequence divergence, because structural variation can appear without sequence diversity. In this work, we explore the impact that conformational diversity has on the relationship between structural and sequence divergence. We find that the extent of conformational diversity can be as high as the maximum structural divergence among families. Also, as expected, conformational diversity impairs the well-established correlation between sequence and structural divergence, which is nosier than previously suggested. However, we found that this noise can be resolved using a priori information coming from the structure-function relationship. We show that protein families with low conformational diversity show a well-correlated relationship between sequence and structural divergence, which is severely reduced in proteins with larger conformational diversity. This lack of correlation could impair TBM results in highly dynamical proteins. Finally, we also find that the presence of order/disorder can provide useful beforehand information for better TBM performance.

show abstract

“…First, we found that the extent of the CD could be as large as the MSD (Fig 1). Conformational diversity is a key concept to understand many processes and mechanisms in protein function, such as enzyme catalysis [49], promiscuity in protein interactions [50], protein-protein recognition [51], signal transduction [52], mechanisms of disease-related mutations [53], immune escape [54], the origin of neurodegenerative diseases [55], protein evolutionary rates [56], conformer-specific substitution patterns [57], the origins of new biological functions [58], molecular motors [59], and co-evolutionary measurements between residues [24,60] (for a recent review please see [17]).…”

Section: Discussionmentioning

confidence: 99%

Homology modeling in a dynamical world

Monzón

Zea

Marino-Buslje

et al. 2017

Preprint

Self Cite

View full text Add to dashboard Cite

A key concept in template-based modeling is the high correlation between sequence and structural divergence, with the practical consequence that homologous proteins that are similar at the sequence level will also be similar at the structural level. However, conformational diversity of the native state will reduce the correlation between structural and sequence divergence, because structural variation can appear without sequence diversity.In this work, we explore the impact that conformational diversity has on the relationship between structural and sequence divergence. We find that the extent of conformational diversity can be as high as the maximum structural divergence among families. Also, as expected, conformational diversity impairs the well-established correlation between sequence and structural divergence, which is nosier than previously suggested. However, we found that this noise can be resolved using a priori information coming from the structure-function relationship.We show that protein families with low conformational diversity show a well-correlated relationship between sequence and structural divergence, which is severely reduced in proteins with larger conformational diversity. This lack of correlation could impair Template-based modelling (TMB) results in highly dynamical proteins. Finally, we also find that the presence of order/disorder can provide useful beforehand information for better TBM performance. Author summaryTemplate-based modelling (TBM) is the most reliable and fastest approach to obtain protein structural models. TBM relies in the high correlation between sequence and structural divergence, with the practical consequence that proteins that are similar at the sequence level will also be similar at the structural level, allowing in this way the selection of the better template to obtain the 3D model of the target sequence. However, protein native state could be described by a collection of conformers in equilibrium where their structural differences are called conformational diversity.In this work, we explore the impact that conformational diversity has on the relationship between structural and sequence divergence. We firstly found that the extent of conformational diversity can be as high as the maximum structural differences reached by families differing in their sequences. In these proteins with higher conformational diversity levels, the well-established correlation between sequence and structural divergence is nosier than previously suggested . CC-BY-NC-ND 4.0 International license peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/135004 doi: bioRxiv preprint first posted online May. 6, 2017; 3 due to the presence of structural change without sequence variation. This lack of correlation could impair TBM results due to the uncertainty in the correct template selection. Finally, we also found that the presence of order/disorder can provide useful beforehand information ...

show abstract

Protein Conformational Diversity Correlates with Evolutionary Rate

Cited by 34 publications

References 31 publications

Parallel dynamics and evolution: Protein conformational fluctuations and assembly reflect evolutionary changes in sequence and structure

Parallel dynamics and evolution: Protein conformational fluctuations and assembly reflect evolutionary changes in sequence and structure

Homology modeling in a dynamical world

Homology modeling in a dynamical world

Contact Info

Product

Resources

About