BackgroundA significant number of proteins have been shown to be intrinsically disordered, meaning that they lack a fixed 3 D structure or contain regions that do not posses a well defined 3 D structure. It has also been proven that a protein's disorder content is related to its function. We have performed an exhaustive analysis and comparison of the disorder content of proteins from prokaryotic organisms (i.e., superkingdoms Archaea and Bacteria) with respect to functional categories they belong to, i.e., Clusters of Orthologous Groups of proteins (COGs) and groups of COGs-Cellular processes (Cp), Information storage and processing (Isp), Metabolism (Me) and Poorly characterized (Pc).We also analyzed the disorder content of proteins with respect to various genomic, metabolic and ecological characteristics of the organism they belong to. We used correlations and association rule mining in order to identify the most confident associations between specific modalities of the characteristics considered and disorder content.ResultsBacteria are shown to have a somewhat higher level of protein disorder than archaea, except for proteins in the Me functional group. It is demonstrated that the Isp and Cp functional groups in particular (L-repair function and N-cell motility and secretion COGs of proteins in specific) possess the highest disorder content, while Me proteins, in general, posses the lowest. Disorder fractions have been confirmed to have the lowest level for the so-called order-promoting amino acids and the highest level for the so-called disorder promoters.For each pair of organism characteristics, specific modalities are identified with the maximum disorder proteins in the corresponding organisms, e.g., high genome size-high GC content organisms, facultative anaerobic-low GC content organisms, aerobic-high genome size organisms, etc. Maximum disorder in archaea is observed for high GC content-low genome size organisms, high GC content-facultative anaerobic or aquatic or mesophilic organisms, etc. Maximum disorder in bacteria is observed for high GC content-high genome size organisms, high genome size-aerobic organisms, etc.Some of the most reliable association rules mined establish relationships between high GC content and high protein disorder, medium GC content and both medium and low protein disorder, anaerobic organisms and medium protein disorder, Gammaproteobacteria and low protein disorder, etc. A web site Prokaryote Disorder Database has been designed and implemented at the address http://bioinfo.matf.bg.ac.rs/disorder, which contains complete results of the analysis of protein disorder performed for 296 prokaryotic completely sequenced genomes.ConclusionsExhaustive disorder analysis has been performed by functional classes of proteins, for a larger dataset of prokaryotic organisms than previously done. Results obtained are well correlated to those previously published, with some extension in the range of disorder level and clear distinction between functional classes of proteins. Wide correlation and...

doi: bioRxiv preprint Cells across all kingdoms of life actively partition molecules between discrete cellular compartments. In Gram-positive bacteria, a thick and highly cross-linked peptidoglycan cell wall separates the bacterial membrane from the extracellular space, imposing a barrier that must be crossed by proteins whose functions require that they be exposed on the bacterial cell surface 1,2 . Some surface-exposed proteins, such as the Listeria monocytogenes actin nucleation-promoting factor ActA 3 , remain associated with the bacterial membrane yet somehow thread through tens of nanometers of dense, cross-linked cell wall to expose their N-terminus on the outer surface 4,5 . Here, we show that entropy can drive the translocation of disordered transmembrane proteins through the Gram-positive cell wall. We develop a physical model predicting that the entropic constraint imposed by a thin periplasm is sufficient to drive translocation of an intrinsically disordered protein like ActA across a porous barrier similar to the cell wall. Consistent with this scenario, we demonstrate experimentally that translocation depends on both the dimensions of the cell envelope and the length of the disordered protein, and that translocation is reversible. We also show that disordered regions from eukaryotic nuclear pore complex proteins are capable of entropy-driven translocation through Gram-positive cell walls. These observations suggest that entropic forces alone, rather than chaperones or chemical energy, are sufficient to drive translocation of certain Gram-positive surface proteins for exposure on the outer surface of the cell wall.Surface-exposed proteins are used by both commensal and pathogenic bacteria to mediate a range of processes that are essential for survival within a mammalian host 6,7 . These hostmicrobe interactions often involve binding of bacterial proteins to host factors that are too large to diffuse through the nanometer-scale pores of the bacterial cell wall 8 . Therefore, such bacterial

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Sequencestructurefunction paradigm has been revolutionized by the discovery of disordered regions and disordered proteins more than two decades ago. While the definition of rigidity is simple with X-ray structures, the notion of flexibility is linked to high experimental B-factors. The definition of disordered regions is more complex as in these same X-ray structures; it is associated to the position of missing residues. Thus a continuum so seems to exist between rigidity, flexibility and disorder. However, it had not been precisely described. In this study, we used an ensemble of disordered proteins (or regions) and, we applied a structural alphabet to analyse their local conformation. This structural alphabet, namely Protein Blocks, had been efficiently used to highlight rigid local domains within flexible regions and so discriminates deformability and mobility concepts. Using an entropy index derived from this structural alphabet, we underlined its interest to measure these local dynamics, and to quantify, for the first time, continuum states from rigidity to flexibility and finally disorder. We also highlight non-disordered regions in the ensemble of disordered proteins in our study.

A dataset of 103 SARS-CoV isolates (101 human patients and 2 palm civets) was investigated on different aspects of genome polymorphism and isolate classification. The number and the distribution of single nucleotide variations (SNVs) and insertions and deletions, with respect to a “profile”, were determined and discussed ("profile" being a sequence containing the most represented letter per position). Distribution of substitution categories per codon positions, as well as synonymous and non-synonymous substitutions in coding regions of annotated isolates, was determined, along with amino acid (a.a.) property changes. Similar analysis was performed for the spike (S) protein in all the isolates (55 of them being predicted for the first time). The ratio Ka/Ks confirmed that the S gene was subjected to the Darwinian selection during virus transmission from animals to humans. Isolates from the dataset were classified according to genome polymorphism and genotypes. Genome polymorphism yields to two groups, one with a small number of SNVs and another with a large number of SNVs, with up to four subgroups with respect to insertions and deletions. We identified three basic nine-locus genotypes: TTTT/TTCGG, CGCC/TTCAT, and TGCC/TTCGT, with four subgenotypes. Both classifications proposed are in accordance with the new insights into possible epidemiological spread, both in space and time.