scholarly journals Molecular recognition features (MoRFs) in three domains of life

2016 ◽  
Vol 12 (3) ◽  
pp. 697-710 ◽  
Author(s):  
Jing Yan ◽  
A. Keith Dunker ◽  
Vladimir N. Uversky ◽  
Lukasz Kurgan
Keyword(s):  
Amino Acid ◽  
Molecular Recognition ◽  
Protein Binding ◽  
Amino Acid Composition ◽  
Acid Composition ◽  
Intrinsically Disordered Protein ◽  
Intrinsically Disordered ◽  
Disordered Protein ◽  
Domains Of Life ◽  
Molecular Recognition Features

MoRFs are widespread intrinsically disordered protein-binding regions that have similar abundance and amino acid composition across the three domains of life.

scholarly journals Analysis of Heterodimeric “Mutual Synergistic Folding”-Complexes

2019 ◽  
Vol 20 (20) ◽  
pp. 5136 ◽  
Author(s):  
Mentes ◽  
Magyar ◽  
Fichó ◽  
Simon
Keyword(s):  
Amino Acid ◽  
Amino Acid Composition ◽  
Acid Composition ◽  
Intrinsically Disordered Proteins ◽  
Driving Forces ◽  
Disordered Proteins ◽  
Subunit Interactions ◽  
Amino Acid Compositions ◽  
Intrinsically Disordered ◽  
Β Sheet

Several intrinsically disordered proteins (IDPs) are capable to adopt stable structures without interacting with a folded partner. When the folding of all interacting partners happens at the same time, coupled with the interaction in a synergistic manner, the process is called Mutual Synergistic Folding (MSF). These complexes represent a discrete subset of IDPs. Recently, we collected information on their complexes and created the MFIB (Mutual Folding Induced by Binding) database. In a previous study, we compared homodimeric MSF complexes with homodimeric and monomeric globular proteins with similar amino acid sequence lengths. We concluded that MSF homodimers, compared to globular homodimeric proteins, have a greater solvent accessible main-chain surface area on the contact surface of the subunits, which becomes buried during dimerization. The main driving force of the folding is the mutual shielding of the water-accessible backbones, but the formation of further intermolecular interactions can also be relevant. In this paper, we will report analyses of heterodimeric MSF complexes. Our results indicate that the amino acid composition of the heterodimeric MSF monomer subunits slightly diverges from globular monomer proteins, while after dimerization, the amino acid composition of the overall MSF complexes becomes more similar to overall amino acid compositions of globular complexes. We found that inter-subunit interactions are strengthened, and additionally to the shielding of the solvent accessible backbone, other factors might play an important role in the stabilization of the heterodimeric structures, likewise energy gain resulting from the interaction of the two subunits with different amino acid compositions. We suggest that the shielding of the β-sheet backbones and the formation of a buried structural core along with the general strengthening of inter-subunit interactions together could be the driving forces of MSF protein structural ordering upon dimerization.

Clusters in an Intrinsically Disordered Protein Create a Protein-Binding Site:  The TolB-Binding Region of Colicin E9†

Biochemistry ◽  
2005 ◽  
Vol 44 (34) ◽  
pp. 11496-11507 ◽  
Author(s):  
Kaeko Tozawa ◽  
Colin J. Macdonald ◽  
Christopher N. Penfold ◽  
Richard James ◽  
Colin Kleanthous ◽  
...  
Keyword(s):  
Protein Binding ◽  
Binding Site ◽  
Intrinsically Disordered Protein ◽  
Protein Binding Site ◽  
Binding Region ◽  
Intrinsically Disordered ◽  
Disordered Protein ◽  
Colicin E9

scholarly journals Molecular Recognition by Templated Folding of an Intrinsically Disordered Protein

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Angelo Toto ◽  
Carlo Camilloni ◽  
Rajanish Giri ◽  
Maurizio Brunori ◽  
Michele Vendruscolo ◽  
...  
Keyword(s):  
Molecular Recognition ◽  
Intrinsically Disordered Protein ◽  
Intrinsically Disordered ◽  
Disordered Protein

scholarly journals Sequence determinants of in cell condensate assembly morphology, dynamics, and oligomerization as measured by number and brightness analysis

2021 ◽  
Author(s):  
Ryan J Emenecker ◽  
Alex S Holehouse ◽  
Lucia Strader
Keyword(s):  
Amino Acid ◽  
Amino Acid Composition ◽  
Acid Composition ◽  
Material Properties ◽  
Oligomeric State ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Brightness Analysis ◽  
Oligomerization Domain

Background: Biomolecular condensates are non-stoichiometric assemblies that are characterized by their capacity to spatially concentrate biomolecules and play a key role in cellular organization. Proteins that drive the formation of biomolecular condensates frequently contain oligomerization domains and intrinsically disordered regions (IDRs), both of which can contribute multivalent interactions that drive higher-order assembly. Our understanding of the relative and temporal contribution of oligomerization domains and IDRs to the material properties of in vivo biomolecular condensates is limited. Similarly, the spatial and temporal dependence of protein oligomeric state inside condensates has been largely unexplored in vivo. Methods: In this study, we combined quantitative microscopy with number and brightness analysis to investigate the aging, material properties, and protein oligomeric state of biomolecular condensates in vivo. Our work is focused on condensates formed by AUXIN RESPONSE FACTOR 19 (ARF19), which is a transcription factor integral to the signaling pathway for the plant hormone auxin. ARF19 contains a large central glutamine-rich IDR and a C-terminal Phox Bem1 (PB1) oligomerization domain and forms cytoplasmic condensates. Results: Our results reveal that the IDR amino acid composition can influence the morphology and material properties of ARF19 condensates. In contrast the distribution of oligomeric species within condensates appears insensitive to the IDR composition. In addition, we identified a relationship between the abundance of higher- and lower-order oligomers within individual condensates and their apparent fluidity. Conclusions: IDR amino acid composition affects condensate morphology and material properties. In ARF condensates, altering the amino acid composition of the IDR did not greatly affect the oligomeric state of proteins within the condensate.

scholarly journals Proteins of generalist and specialist pathogens differ in their amino acid composition

2018 ◽  
Vol 1 (4) ◽  
pp. e201800017 ◽  
Author(s):  
Luz P Blanco ◽  
Bryan L Payne ◽  
Felix Feyertag ◽  
David Alvarez-Ponce
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Composition ◽  
Host Range ◽  
Acid Composition ◽  
Secreted Proteins ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Cytoplasmic Proteins ◽  
Disordered Regions

Pathogens differ in their host specificities, with species infecting a unique host (specialist pathogens) and others having a wide host range (generalists). Molecular determinants of pathogen’s host range remain poorly understood. Secreted proteins of generalist pathogens are expected to have a broader range of intermolecular interactions (i.e., higher promiscuity) compared with their specialist counterparts. We hypothesize that this increased promiscuity of generalist secretomes may be based on an elevated content of primitive amino acids and intrinsically disordered regions, as these features are known to increase protein flexibility and interactivity. Here, we measure the proportion of primitive amino acids and percentage of intrinsically disordered residues in secreted, membrane, and cytoplasmic proteins from pathogens with different host specificity. Supporting our prediction, there is a significant general enrichment for primitive amino acids and intrinsically disordered regions in proteins from generalists compared to specialists, particularly among secreted proteins in prokaryotes. Our findings support our hypothesis that secreted proteins' amino acid composition and disordered content influence the pathogens' host range.

scholarly journals A molecular recognition feature mediates ribosome-induced SRP-receptor assembly during protein targeting

2019 ◽  
Vol 218 (10) ◽  
pp. 3307-3319 ◽  
Author(s):  
Yu-Hsien Hwang Fu ◽  
Sowmya Chandrasekar ◽  
Jae Ho Lee ◽  
Shu-ou Shan
Keyword(s):  
Molecular Recognition ◽  
Protein Targeting ◽  
Signal Recognition Particle ◽  
Intrinsically Disordered Protein ◽  
Signal Recognition ◽  
Cellular Functions ◽  
Intrinsically Disordered ◽  
Disordered Protein ◽  
Linker Domain ◽  
Receptor Assembly

Molecular recognition features (MoRFs) provide interaction motifs in intrinsically disordered protein regions to mediate diverse cellular functions. Here we report that a MoRF element, located in the disordered linker domain of the mammalian signal recognition particle (SRP) receptor and conserved among eukaryotes, plays an essential role in sensing the ribosome during cotranslational protein targeting to the endoplasmic reticulum. Loss of the MoRF in the SRP receptor (SR) largely abolishes the ability of the ribosome to activate SRP-SR assembly and impairs cotranslational protein targeting. These results demonstrate a novel role for MoRF elements and provide a mechanism for the ribosome-induced activation of the mammalian SRP pathway. Kinetic analyses and comparison with the bacterial SRP further suggest that the SR MoRF functionally replaces the essential GNRA tetraloop in the bacterial SRP RNA, providing an example for the replacement of RNA function by proteins during the evolution of ancient ribonucleoprotein particles.

scholarly journals Sequence determinants of in cell condensate morphology, dynamics, and oligomerization as measured by number and brightness analysis

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Ryan J. Emenecker ◽  
Alex S. Holehouse ◽  
Lucia C. Strader
Keyword(s):  
Amino Acid ◽  
Amino Acid Composition ◽  
Acid Composition ◽  
Material Properties ◽  
Auxin Signaling ◽  
Oligomeric State ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Brightness Analysis

Abstract Background Biomolecular condensates are non-stoichiometric assemblies that are characterized by their capacity to spatially concentrate biomolecules and play a key role in cellular organization. Proteins that drive the formation of biomolecular condensates frequently contain oligomerization domains and intrinsically disordered regions (IDRs), both of which can contribute multivalent interactions that drive higher-order assembly. Our understanding of the relative and temporal contribution of oligomerization domains and IDRs to the material properties of in vivo biomolecular condensates is limited. Similarly, the spatial and temporal dependence of protein oligomeric state inside condensates has been largely unexplored in vivo. Methods In this study, we combined quantitative microscopy with number and brightness analysis to investigate the aging, material properties, and protein oligomeric state of biomolecular condensates in vivo. Our work is focused on condensates formed by AUXIN RESPONSE FACTOR 19 (ARF19), a transcription factor integral to the auxin signaling pathway in plants. ARF19 contains a large central glutamine-rich IDR and a C-terminal Phox Bem1 (PB1) oligomerization domain and forms cytoplasmic condensates. Results Our results reveal that the IDR amino acid composition can influence the morphology and material properties of ARF19 condensates. In contrast the distribution of oligomeric species within condensates appears insensitive to the IDR composition. In addition, we identified a relationship between the abundance of higher- and lower-order oligomers within individual condensates and their apparent fluidity. Conclusions IDR amino acid composition affects condensate morphology and material properties. In ARF condensates, altering the amino acid composition of the IDR did not greatly affect the oligomeric state of proteins within the condensate.

scholarly journals LCD-Composer: an intuitive, composition-centric method enabling the identification and detailed functional mapping of low-complexity domains

2021 ◽  
Vol 3 (2) ◽  
Author(s):  
Sean M Cascarina ◽  
David C King ◽  
Erin Osborne Nishimura ◽  
Eric D Ross
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Composition ◽  
Acid Composition ◽  
Large Scale ◽  
Low Complexity ◽  
Functional Mapping ◽  
Small Subset ◽  
Biologically Relevant ◽  
Domains Of Life

Abstract Low complexity domains (LCDs) in proteins are regions predominantly composed of a small subset of the possible amino acids. LCDs are involved in a variety of normal and pathological processes across all domains of life. Existing methods define LCDs using information-theoretical complexity thresholds, sequence alignment with repetitive regions, or statistical overrepresentation of amino acids relative to whole-proteome frequencies. While these methods have proven valuable, they are all indirectly quantifying amino acid composition, which is the fundamental and biologically-relevant feature related to protein sequence complexity. Here, we present a new computational tool, LCD-Composer, that directly identifies LCDs based on amino acid composition and linear amino acid dispersion. Using LCD-Composer's default parameters, we identified simple LCDs across all organisms available through UniProt and provide the resulting data in an accessible form as a resource. Furthermore, we describe large-scale differences between organisms from different domains of life and explore organisms with extreme LCD content for different LCD classes. Finally, we illustrate the versatility and specificity achievable with LCD-Composer by identifying diverse classes of LCDs using both simple and multifaceted composition criteria. We demonstrate that the ability to dissect LCDs based on these multifaceted criteria enhances the functional mapping and classification of LCDs.

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