Molecular recognition features (MoRFs) in three domains of life

Abstract

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

Mycobacterium tuberculosisComplex Exhibits Lineage-Specific Variations Affecting Protein Ductility and Epitope Recognition

“…Research of the past decade and a half has provided valuable information about intrinsically disordered/ductile proteins (IDPs) and regions (IDRs) as well as their role in diseases (van der Lee et al 2014; Yan et al 2016). IDPs and IDRs are characterized by a number of specific features that distinguish them from those of ordered proteins and domains and make them predictable (He et al 2009).…”

“…To know in detail the implications of mutations in ductile regions the attention was focused in well-annotated proteins with longer disordered segments (L > 30) because these regions are normally associated with high confidence to particular functions (Radivojac et al 2007; Orosz and Ovádi, 2011; Yan et al 2016). Twenty-one of these well-annotated proteins have mutations along their sequences.…”

“…It is known that IDRs in proteins are relevant in molecular recognition and protein-protein interactions (Vacic et al 2007; Yan et al 2016). This fact makes that these regions can have an important role in bacterial pathogenesis and virulence.…”

Resolving the ambiguity: Making sense of intrinsic disorder when PDB structures disagree

“…In order to predict binding propensity and the presence of MoRFs, we used the DNA, RNA, and protein binding predictor DisoRDPbind, as well as the MoRF predictors ANCHOR and a new fast version of MoRFpred . All disorder and binding scores were treated as binary (either ordered or disordered), with the threshold set based on published materials of the predictor in question.…”

How disordered is my protein and what is its disorder for? A guide through the “dark side” of the protein universe

“…Since short regions of predicted order embedded within longer regions of predicted disorder have been shown to correspond to binding sites that fold upon complex formation, 85,86 several specialized tools that identify short regions that undergo disorder-to-order transitions on binding (known as Molecular Recognition Features, MoRFs) were developed. [86][87][88][89][90][91] Two models complementary to MoRF-like interactions, the Short Linear Motif (SLiM) and the Eukaryotic Linear Motif (ELM), are based on sequence motifs that are recognized by peptide recognition domains. 92 A different approach is taken by the ANCHOR model, which identifies segments of disordered regions that are likely to fold in conjunction with a globular binding partner.…”