BIAPSS: A Comprehensive Physicochemical Analyzer of Proteins Undergoing Liquid–Liquid Phase Separation

Abstract

The liquid–liquid phase separation (LLPS) of biomolecules is a phenomenon which is nowadays recognized as the driving force for the biogenesis of numerous functional membraneless organelles and cellular bodies. The interplay between the protein primary sequence and phase separation remains poorly understood, despite intensive research. To uncover the sequence-encoded signals of protein capable of undergoing LLPS, we developed a novel web platform named BIAPSS (Bioinformatics Analysis of LLPS Sequences). This web server provides on-the-fly analysis, visualization, and interpretation of the physicochemical and structural features for the superset of curated LLPS proteins.

Liaisons dangereuses: Intrinsic Disorder in Cellular Proteins Recruited to Viral Infection-Related Biocondensates

“…CAD directly interacts with the EBOV N protein, with N being sufficient to recruit CAD into IBs via the glutaminase (GLN) domain of the latter. 18 Mitogen-activated protein kinase 14 (MAPK14) or p38MAPKα is a key regulator of cellular inflammatory and stress responses. RSV induces the sequestration of p38MAPKα in IBs resulting in the accumulation of a downstream signaling substrate, MAPK-activated protein kinase 2 (MAPK2).…”

“…The sequence degeneracy of IDPs/IDRs, favoring low complexity, encodes residue types and/or short motifs that favor three-dimensional networking of protein chains, and thus behave as stickers [18]. This ability is further amplified by their structural flexibility, conformational dynamics [19], and the general accessibility of IDRs to the enzymes catalyzing various PTMs [20] that ultimately impact their charge and hydrophobicity.…”

Effects of Mass Change on Liquid–Liquid Phase Separation of the RNA-Binding Protein Fused in Sarcoma

“…Uversky, Dunker et al opened the door to the investigation of IDPs [ 21 , 22 ], and Uversky et al firstly proposed that IDPs serve as important drivers of intracellular LLPS based on the comprehensive assessment of protein intrinsic disorder predisposition by in silico predictors [ 23 ]. Recently, Uversky et al developed a novel web platform named BIAPSS, which can uncover the sequence-encoded signals of proteins capable of undergoing LLPS [ 24 ]. IDRs are typically enriched in charged, polar, and/or aromatic amino acids and contain amino acids such as glycine and proline that may convey some structural information [ 6 ].…”

Biological Liquid–Liquid Phase Separation, Biomolecular Condensates, and Membraneless Organelles: Now You See Me, Now You Don’t

“…Aleksandra E. Badaczewska-Dawid, Vladimir N. Uversky, and Davit A. Potoyan reported the development of a convenient web platform, Bioinformatics Analysis of LLPS Sequences (BIAPSS) [22]. The need for such a tool is based on the premises that despite a broad acceptance of the importance of biological LLPS, MLOs, and BMCs, there is a remarkable gap in the current knowledge which prevents a complete understanding of the sequence "codes" of phase separation required for the design of new phase-separating sequences of fundamental, medical, and technological importance.…”

“…The need for such a tool is based on the premises that despite a broad acceptance of the importance of biological LLPS, MLOs, and BMCs, there is a remarkable gap in the current knowledge which prevents a complete understanding of the sequence "codes" of phase separation required for the design of new phase-separating sequences of fundamental, medical, and technological importance. Therefore, the goals of this tool were to enhance apprehension of the interplay between the primary sequences of proteins and their capability to undergo spontaneous LLPS and thereby to uncover the sequence-encoded signals of the LLPS potential and related biogenesis of numerous functional MLOs and cellular bodies [22]. Researchers can use this web server in on-the-fly analysis as BIAPSS provides a useful tool for the visualization and interpretation of the physicochemical and structural features for the superset of curated LLPS proteins [22].…”