The alphabet of intrinsic disorder

Theillet, François‐Xavier; Kalmár, Lajos; Tompa, Péter; Han, Kyou‐Hoon; Selenko, Philipp; Dunker, A. Keith; Daughdrill, Gary W.; Uversky, Vladimir N.

doi:10.4161/idp.24360

Cited by 228 publications

(159 citation statements)

References 201 publications

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“…The highest positional propensities of proline were found in the helical peptides when a proline is situated at the N-terminus of a helix [23,24]. Without much surprise one finds that IDPs have many disorder-promoting proline residues [25,26]. Furthermore an interesting point was revealed during a recent examination of the amino acid sequences for the  type IDPs that prolines are more frequently observed in the flanking regions of PreSMos than other regions of IDPs.…”

Section: Introductionmentioning

confidence: 91%

Contribution of proline to the pre-structuring tendency of transient helical secondary structure elements in intrinsically disordered proteins

Lee

Kalmár

Xue

et al. 2014

Biochimica et Biophysica Acta (BBA) - General Subjects

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Section: Introductionmentioning

confidence: 91%

Contribution of proline to the pre-structuring tendency of transient helical secondary structure elements in intrinsically disordered proteins

Lee

Kalmár

Xue

et al. 2014

Biochimica et Biophysica Acta (BBA) - General Subjects

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“…Proline can be found at the N termini, but not in the middle, of the ␣-helices (44). Among all amino acids, proline has the lowest helix propensity (45) and the highest disorder propensity (46). For these reasons, proline is known to break or kink helical structures.…”

Section: Discussionmentioning

confidence: 99%

In Vitro Activity of Five Quinolones and Analysis of the Quinolone Resistance-Determining Regions of gyrA , gyrB , parC , and parE in Ureaplasma parvum and Ureaplasma urealyticum Clinical Isolates from Perinatal Patients in Japan

Kawai

Nakura

Wakimoto

et al. 2015

Antimicrob Agents Chemother

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g Ureaplasma spp. cause several disorders, such as nongonococcal urethritis, miscarriage, and preterm delivery with lung infections in neonates, characterized by pathological chorioamnionitis in the placenta. Although reports on antibiotic resistance in Ureaplasma are on the rise, reports on quinolone-resistant Ureaplasma infections in Japan are limited. The purpose of this study was to determine susceptibilities to five quinolones of Ureaplasma urealyticum and Ureaplasma parvum isolated from perinatal samples in Japan and to characterize the quinolone resistance-determining regions in the gyrA, gyrB, parC, and parE genes. Out of 28 clinical Ureaplasma strains, we isolated 9 with high MICs of quinolones and found a single parC gene mutation, resulting in the change S83L. Among 158 samples, the ParC S83L mutation was found in 37 samples (23.4%), including 1 sample harboring a ParC S83L-GyrB P462S double mutant. Novel mutations of ureaplasmal ParC (S83W and S84P) were independently found in one of the samples. Homology modeling of the ParC S83W mutant suggested steric hindrance of the quinolone-binding pocket (QBP), and de novo prediction of peptide structures revealed that the ParC S84P may break/kink the formation of the ␣4 helix in the QBP. Further investigations are required to unravel the extent and mechanism of antibiotic resistance of Ureaplasma spp. in Japan.Ureaplasma spp. are among the smallest self-replicating organisms, in terms of both genome size and cellular dimensions. They lack cell walls and are thus resistant to penicillin and other ␤-lactams. These organisms exist in association with eukaryotic cells, mainly colonizing mucosal surfaces of the respiratory and urogenital tracts (1, 2). Ureaplasma spp. are common inhabitants of the lower genital tract and can be isolated from 40% to 80% of women of child-bearing age (1, 3). Ureaplasma spp. have been associated with a range of pathologies, including nongonococcal urethritis (NGU), miscarriage, preterm delivery, neonatal pneumonia, and chronic lung disease in preterm neonates (4, 5). Many reports have suggested that Ureaplasma parvum and/or Ureaplasma urealyticum may be associated with urogenital infections, infertility, and adverse pregnancy outcomes (6). Regarding the management of ureaplasmal infections, only a limited number of reports are available on the surveillance of antimicrobial resistance in clinical Ureaplasma strains, which is crucial for providing therapy empirically (6). The treatment of ureaplasmal infections is limited to tetracyclines, macrolides, and quinolones (5, 7). Resistance to all the three antibiotic classes in clinical Ureaplasma isolates has been documented, with unique nucleic acid substitutions identified as potential molecular mechanisms for each (5,(8)(9)(10).Quinolones are used for treating urogenital infections and interact in bacteria with the type II topoisomerases DNA gyrase and topoisomerase IV, both of which are composed of two A and two B subunits; these subunits are encoded by the gyrA and gyrB genes for DNA...

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“…The former two are depleted in IDRs and all three amino acid types have a relatively high propensity for formation of strands. Both, the α-and β-MoRFs are depleted in Proline and Glycine, which are considered as disorder-promoting residues 10,106 , are known as major structure breaker residues and are commonly found at the ends of regular secondary structure elements 107 . For example, since Proline peptide bonds exhibit structural features that differ substantially from those of other residues, also because they do not contain backbone amide hydrogen atoms at physiological pH, they do not form stabilizing hydrogen bonds in α-helices or β-sheets 108,109 .…”

Section: Amino Acid Composition Of Morf and Disordered Regionsmentioning

confidence: 99%

Molecular recognition features (MoRFs) in three domains of life

et al. 2016

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Intrinsically disordered proteins and protein regions offer numerous advantages in the context of protein-protein interactions when compared to the structured proteins and domains. These advantages include ability to interact with multiple partners, to fold into different conformations when bound to different partners, and to undergo disorder-to-order transitions concomitant with their functional activity. Molecular Recognition Features (MoRFs) are widespread elements located in disordered regions that undergo disorder-to-order transition upon binding to their protein partners. We characterize abundance, composition, and functions of MoRFs and their association with the disordered regions across 868 species spread across Eukaryota, Bacteria and Archaea. We found that although disorder is substantially elevated in Eukaryota, MoRFs have similar abundance and amino acid composition across the three domains of life. The abundance of MoRFs is highly correlated with the amount of intrinsic disorder in Bacteria and Archaea but only modestly correlated in Eukaryota. Proteins with MoRFs have significantly more disorder and MoRFs are present in many disordered regions, with Eukaryota having more MoRF-free disordered regions. MoRF-containing proteins are enriched in the ribosome, nucleus, nucleolus and microtubule and are involved in translation, protein transport, protein folding, and interactions with DNAs. Our insights into the nature and function of MoRFs enhance our understanding of the mechanisms underlying the disorder-to-order transition and protein-protein recognition and interactions. The fMoRFpred method that we used to annotate MoRFs is available at

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The alphabet of intrinsic disorder

Cited by 228 publications

References 201 publications

Contribution of proline to the pre-structuring tendency of transient helical secondary structure elements in intrinsically disordered proteins

Contribution of proline to the pre-structuring tendency of transient helical secondary structure elements in intrinsically disordered proteins

In Vitro Activity of Five Quinolones and Analysis of the Quinolone Resistance-Determining Regions of gyrA , gyrB , parC , and parE in Ureaplasma parvum and Ureaplasma urealyticum Clinical Isolates from Perinatal Patients in Japan

Molecular recognition features (MoRFs) in three domains of life

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