Fig. 2
From: Biomolecular condensates: insights into early and late steps of the HIV-1 replication cycle
Functional disorder analysis of human Nup153 protein (UniProt ID: P49790). A Per-residue disorder profile generated by RIDAO [138]. Per-residue intrinsic disorder profiles generated by PONDR® VLXT, PONDR® VL3, PONDR® VSL2, PONDR® FIT, IUPred_long and IUPred_short. Mean disorder profile (MDP) is calculated by averaging of the disorder profiles of individual predictors. Light pink shade represents MDP error distribution. The thin black line at the disorder score of 0.5 is the threshold between order and disorder, where residues/regions above 0.5 are disordered and residues/regions below 0.5 are ordered. The thin dashed line at the disorder score of 0.15 is the threshold between order and flexibility, where residues/regions above 0.15 are flexible and residues/regions below 0.15 are highly ordered. B Functional disorder profile generated by the D2P2 platform [139]. Here, the IDR localization predicted by IUPred, PONDR® VLXT, PONDR® VSL2, PrDOS, PV2, and ESpritz are shown by 9 differently colored bars on the top of the plot, whereas the blue-green-white bar in the middle of the plots shows the agreement between the outputs of these disorder predictors, with disordered regions by consensus being shown by blue and green. The two lines with colored and numbered bars above the disorder consensus bar show the positions of functional SCOP domains [140, 141] predicted using the SUPERFAMILY predictor [142]. Positions of the predicted disorder-based binding sites (MoRF regions) identified by the ANCHOR algorithm are shown by yellow zigzagged bars [143]. Locations of the sites of different PTMs identified by the PhosphoSitePlus platform [144] are shown at the bottom of the plot by the differently colored circles. Here, phosphorylation, ubiquitylation, acetylation, glycosylation and methylation sites are shown by red, violet, yellow, orange and blue circles with the letters P, U, A, G, and M, respectively. An interactive profile generated for human Nup153 protein by D2P2 can be found at the following link: https://d2p2.pro/view/sequence/up/P49790. C Evaluation of LLPS predisposition and existence of regions with context-dependent disorder [145]. Top plot represents sequence distribution of the probability of forming a droplet state through liquid–liquid phase separation (pLLPS). Proteins with pLLPS ≥ 0.60 are droplet-drivers, which can spontaneously undergo liquid–liquid phase separation. Droplet-client proteins have pLLPS < 0.60, but possess droplet-promoting regions (DPRs), which can induce their partitioning into condensates. Positions of DPRs (which contain residues with pDP ≥ 0.60 capable to promote liquid–liquid phase separation) are shown by blue bar. Positions of aggregation hot-spots that drive aggregation of condensates are displayed by orange boxes. These regions are droplet-promoting (pDP ≥ 0.60) and exhibit high interaction mode divergence (SBIND ≥ 2.2) making them sensitive to the cellular context. The bottom plot shows sequence distribution of the SBIND values that characterize the ability of residues to switch between different binding modes. These are computed as Shannon entropy values of the binding mode distribution [146]. Plot also shows regions with context-dependent interactions that change protein interaction behavior and binding modes under different cellular conditions. These residues can be ordered or disordered with SBIND ≥ 2.25. D Model of the CPSF6 3D structure generated by AlphaFold [147]. Structure is colored based on the AlphaFold-generated per-residue confidence score (predicted local distance difference test, pLDDT) values, where orange, yellow, cyan, and blue colors correspond to the segments predicted by AlphaFold with very high very low (pLDDT < 50), low (70 > pLDDT > 50), high (90 > pLDDT > 70), and (pLDDT > 90) confidence