INTRODUCTION
The protein structure-function paradigm is a cornerstone of molecular biology, offering a mechanistic understanding of processes ranging from enzyme catalysis, signal transduction to molecular recognition and allosteric regulation. Underlying this paradigm is the assumption that proteins become functional by assuming a well-defined structure, typically described by the coordinates of all its atoms. A solid foundation of this view is provided by the 130 000 structures of proteins and complexes in the Protein Data Bank, PDB (1). However, it is increasingly recognized that many proteins do not obey this rule. Intrinsically disordered proteins (IDPs) or regions (IDRs) are devoid of order in their native unbound state (2-4). Intrinsic disorder is prevalent in the human proteome (5), appears to play important signaling and regulatory roles (2) and is frequently involved in disease (6). The discovery of intrinsic disorder and its prevalence and functional importance is transforming the field of molecular biology. As intrinsic disorder is emerging as a general phenomenon, databases are collecting and presenting disorder related data in a systematic manner. MobiDB has been a major contributor by providing consensus predictions and functional annotations for all UniProt proteins, driving the field ahead (7,8). The MobiDB upgrade we present in this paper is essential for several reasons.
There is a rapid advance in the functional understanding of intrinsic disorder. The functional classification of IDPs/IDRs is becoming ever more elaborate, with several newly recognized functional mechanisms (9). For example, the central role of intrinsic disorder in the formation of membraneless organelles, such as nucleoli and stress granules, by liquid-liquid phase separation has been characterized recently (10-13). A wide range of experimental observations on the structure-function relationship of IDPs/IDRs is furthering our understanding of disordered states and of the manners in which they function (14-16). These developments have also played a central role in the recent update of the DisProt database (17), the central repository of experimentally characterized IDPs and IDRs. The re-curated version of this database contains experimental observations of disorder for more than 800 protein entries and a renewed functional ontology schema. The experimental evidence on which it rests has also been significantly augmented to include a broad range of biophysical techniques. DisProt is the basis for most developments in disorder predictors (18,19), and its recent update is a major motivation for a new version of MobiDB.
You are watching: A Database Of Protein Disorder And Mobility Annotations
See more : Are Factors Of Prodcution Mobile In Heckscher Ohlin Theory
Additional developments in the field make this release timely. A major source of intrinsic disorder is the identification of residues with missing atomic coordinates in the PDB, which can now be augmented by cryo-electron microscopy (cryo-EM) data. This is having a tremendous impact on structural biology (20,21). Structural descriptions of IDPs and IDRs under physiological conditions have also greatly advanced and are starting to appear in dedicated databases such as IDEAL (22), DIBS (23) and MFIB (24). IDPs and IDRs can perform key roles in molecular recognition by folding upon binding of short linear motifs (SLiMs) covered in the ELM database (25). Generally, the full functional characterization of IDPs and IDRs requires the description not just of their free (disordered) states (26,27), but also of their residual dynamics in the bound states (28). Fuzzy (disordered) complexes can be found in FuzDB (29) and structural ensembles describing the free form (30) in the protein ensemble database (PED (31)). Techniques such as in-cell Nuclear magnetic resonance (NMR) spectroscopy (32,33) and single-molecule fluorescence (34) will soon help study these structures in the physiological state. In reflection of all these developments, we are now launching a significantly updated version of our database, MobiDB 3.0. The new version incorporates additional curated data from specialized databases. Novel annotation features include disorder derived from publicly available NMR chemical shift data (35) and an extended list of predictors. Database searches are facilitated by an improved search algorithm, pre-calculated data and new sections in the database.
Source: https://tholansonnha.com
Category: mobile
