Significance Across the Tree of Life, life’s phenotypic diversity has been accompanied by a massive expansion protein universe. Compared with simple prokaryotes that harbor thousands proteins, plants and animals hundreds proteins are also longer, multidomain, comprise variety folds fold combinations, repeated segments, beta-rich architectures make them prone to misfolding aggregation. Surprisingly, relative representation core chaperones, those dedicated maintaining folding quality these...

Abstract Are there any generalized molecular principles of thermal adaptation? Here, integrating the concepts structural bioinformatics, sequence analysis, and classical knot theory, we develop a robust computational framework that seeks for mechanisms adaptation by comparing orthologous mesophilic‐thermophilic mesophilic‐hyperthermophilic proteins remarkable topological similarities, still leads us to context‐independent results. A comprehensive analysis 4741 high‐resolution, non‐redundant...

Biological systems can gain complexity over time. While some of these transitions are likely driven by natural selection, the extent to which they occur without providing an adaptive benefit is unknown. At molecular level, one example heteromeric complexes replacing homomeric ones following gene duplication. Here, we build a biophysical model and simulate evolution homodimers heterodimers duplication using distributions mutational effects inferred from available protein structures. We keep...

Homomeric proteins are ubiquitous and mediate myriads of cellular functions. When a gene encoding homomer duplicates, the resulting paralogs can either form distinct homomers, or evolve into heteromer containing both paralogs. While such events have extensively shaped proteomes, molecular mechanisms driving these fates their associated functional consequences remain largely unknown. Here, we conducted comprehensive phylogenomic analysis tracing duplication histories 7,377 human across...

ABSTRACT The assembly of proteins into functional complexes is critical to life’s processes. While textbooks depict complex as occurring between fully synthesized proteins, we know today that thousands in the human proteome assemble co-translationally during their synthesis. Why this process takes place, however, remains unknown. We show co-translational governed by biophysical and structural characteristics protein complex, involves mutually stabilized, intertwined subunits. Consequently,...

Oligomeric proteins are central to life. Duplication and divergence of their genes is a key evolutionary driver, also because duplications can yield very different outcomes. Given homomeric ancestor, duplication two paralogs that form distinct complexes, or heteromeric complex comprising both paralogs. Alternatively, one paralog remains homomer while the other acquires new partner. However, so far, conflicting trends have been noted with respect which fate dominates, primarily methods...

Change in folding kinetics of globular proteins upon point mutation is crucial to a wide spectrum biological research, such as protein misfolding, toxicity, and aggregations. Here we seek address whether residue-level coevolutionary information can be informative rate changes mutations. Generating networks proteins, analyze three parameters: relative coevolution order (rCEO), network density (ND), characteristic path length (CPL). A considered equivalent node deletion this respective...

Here we compare the structural and evolutionary attributes of Thermus thermophilus Escherichia coli small ribosomal subunits (SSU). Our results indicate that with few exceptions, thermophilic 16S RNA (16S rRNA) is densely packed compared to mesophilic at most analogous spatial regions. In addition, have located species-specific cavity clusters (SSCCs) in both species. E. SSCCs are numerous larger T. SSCCs, which again indicates rRNA. Thermophilic proteins (r-proteins) longer disordered...

Folding rates (ln k f ) of globular proteins correlate with their biophysical properties, but relationship between ln and patterns sequence evolution remains elusive. We introduce ‘relative co‐evolution order’ ( rCEO as length‐normalized average primary chain separation co‐evolving pairs (CEPs), which negatively correlates . In addition to in native 3D contact, indirectly connected structurally remote CEPs probably also play critical roles protein folding. Correlation is stronger multi‐state...

AbstractUsing the available crystal structures of 50S ribosomal subunits from three prokaryotic species: Escherichia coli (mesophilic), Thermus thermophilus (thermophilic), and Haloarcula marismortui (halophilic), we have analyzed different structural features RNAs (rRNAs), proteins, their interfaces. We correlated these with environmental adaptation strategies corresponding species. While dense intra-rRNA packing is observed in thermophilic, loose halophilic (both compared to mesophilic)....

Precise control of protein and messenger RNA (mRNA) degradation is essential for cellular metabolism homeostasis. Controlled specific both molecular species necessitates their engagements with the respective machineries; this engagement involves a disordered/unstructured segment substrate traversing tunnel machinery accessing catalytic sites. However, while factors influencing have been extensively explored on genome scale, in multiple organisms, such comprehensive understanding remains...

ABSTRACT Is the order in which biomolecular subunits self‐assemble into functional macromolecular complexes imprinted their sequence‐space? Here, we demonstrate that temporal of complex self‐assembly can be efficiently captured using landscape residue‐level coevolutionary constraints. This predictive power constraints is irrespective structural, functional, and phylogenetic classification stoichiometry quaternary arrangement constituent monomers. Combining this result with a number...

ABSTRACT Across the Tree of Life (ToL), complexity proteomes varies widely. Our systematic analysis depicts that from simplest archaea to mammals, total number proteins per proteome expanded ~200-fold. Individual also became larger, and multi-domain ~50-fold. Apart duplication divergence existing proteins, completely new were born. Along ToL, different folds ~5-fold fold-combinations ~20-fold. Proteins prone misfolding aggregation, such as repeat beta-rich proliferated ~600-fold,...

Understanding the molecular evolution of macromolecular complexes in light their structure, assembly, and stability is central importance. Here, we address how modular organization native contacts shapes selection pressure on individual residue sites ribosomal complexes. The bacterial complex represented as a contact network where nodes represent amino acid/nucleotide residues edges van der Waals interactions. We find statistically overrepresented acid-nucleotide (OaantC, one acid or...

Abstract Do coding and regulatory segments of a gene co‐evolve with each‐other? Seeking answers to this question, here we analyze the case Escherichia coli ribosomal protein S15, that represses its own translation by specifically binding messenger RNA (rpsO mRNA) stabilizing pseudoknot structure at upstream untranslated region, thus trapping ribosome into an incomplete initiation complex. In absence S1 recognizes rpsO promotes melting very pseudoknot. We employ robust statistical method...

Abstract Biological systems can gain complexity over time. While some of these transitions are likely driven by natural selection, the extent to which they occur without providing an adaptive benefit is unknown. At molecular level, one example heteromeric complexes replacing homomeric ones following gene duplication. Here, we build a biophysical model and simulate evolution homodimers heterodimers duplication using distributions mutational effects inferred from available protein structures....

Abstract Oligomeric proteins are central to life. Duplication and divergence of their genes is a key evolutionary driver, also because duplications can yield very different outcomes. Given homomeric ancestor, duplication two paralogs that form distinct complexes, or heteromeric complex comprising both paralogs. Alternatively, one paralog remains homomer while the other acquires new partner. However, so far, conflicting trends have been noted with respect which fate dominates, primarily...