Functional fragments of disorder in outer membrane β barrel proteins

Abstract

The traditional view of “sequence–structure–function” has been amended by the discovery of intrinsically disordered proteins. Almost 50% of PDB structures are now known to have one or more regions of disorder, which are involved in diverse functions. These regions typically possess low aromatic content and sequence complexity as well as high net charge and flexibility. In this study, we examined the composition and contribution of intrinsic disorder in outer membrane β barrel protein functions. Our systematic analysis to find the dual personality (DP) fragments, which often function by disorder–order transitions, revealed the presence of 61 DP fragments with 234 residues in β barrel trans membrane protein structures. It was found that though the disorder is more prevalent in the periplasmic regions, most of the residues which undergo disorder–order transitions are found in the extracellular regions. For example, the calcium binding sites in BtuB protein are found to undergo disorder to order transition upon binding calcium. The conformational change in the cell receptor binding site of the OpcA protein, which is important in host cell interactions of N. meningitidis, was also found to be due to the disorder–order transitions occurring in the presence of the ligand. The natively disordered nature of DP fragments makes it more appropriate to call them “functional fragments of disorder.” The present study provides insight into the roles played by intrinsically disordered regions in outer membrane protein functions.

Sequence fingerprints distinguish erroneous from correct predictions of intrinsically disordered protein regions

“…Similarity and dissimilarity analysis have been reported to understand the characteristics of ordered and natively disordered regions (Romero et al, 2001). Weakness in prediction of IDPs and IDRs are due to various factors like amino acid composition, sequence length, sequence repeats and sequence entropy etc., (Kurup, Dunker & Krishnaswamy, 2013). Several disorder predictors have been developed by using different theories such as pseudo amino acid composition, neural networks and machine learning respectively which are discussed in a review by Dosztanyi et al,(2007).…”

Sequence fingerprints distinguish erroneous from correct predictions of Intrinsically Disordered Protein Regions

“…Similarity and dissimilarity analysis have been reported to understand the characteristics of ordered and natively disordered regions (Romero et al, 2001). Weakness in prediction of IDPs and IDRs are due to various factors like amino acid composition, sequence length, sequence repeats and sequence entropy etc., (Kurup, Dunker & Krishnaswamy, 2013). Several disorder predictors have been developed by using different theories such as pseudo amino acid composition, neural networks and machine learning respectively which are discussed in a review by Dosztanyi et al,(2007).…”

Sequence and structural analysis of fibronectin‐binding protein reveals importance of multiple intrinsic disordered tandem repeats

“…Some novel tandem repeats (a region of the protein sequence that occurs more than once in tandem) are identified in cell surface proteins which suggest that sequence patterns in the repeats involve a mechanism to provide a regular array for spatial arrangement, structural packing, or interactions with target molecules . Interestingly, many reports in the literature deal with the functional consequences of sequence repeats, and it was shown that most of the sequence repeats are unstructured or intrinsically disordered . Intrinsically disordered regions (IDRs) are important components of proteins which help to undertake different interactions with different consequence .…”

“…22,23 Interestingly, many reports in the literature deal with the functional consequences of sequence repeats, and it was shown that most of the sequence repeats are unstructured or intrinsically disordered. [24][25][26] Intrinsically disordered regions (IDRs) are important components of proteins which help to undertake different interactions with different consequence. 27 IDRs are polypeptide segments without sufficient hydrophobic amino acid residues to form folded compact structure; instead, they are flexible and mainly made up of polar or charged amino acids.…”