Structure and sequence analyses of Bacteroides proteins BVU_4064 and BF1687 reveal presence of two novel predominantly-beta domains, predicted to be involved in lipid and cell surface interactions.

BackgroundN-terminal domains of BVU_4064 and BF1687 proteins from Bacteroides vulgatus and Bacteroides fragilis respectively are members of the Pfam family PF12985 (DUF3869). Proteins containing a domain from this family can be found in most Bacteroides species and, in large numbers, in all human gut microbiome samples. Both BVU_4064 and BF1687 proteins have a consensus lipobox motif implying they are anchored to the membrane, but their functions are otherwise unknown. The C-terminal half of BVU_4064 is assigned to protein family PF12986 (DUF3870); the equivalent part of BF1687 was unclassified.ResultsCrystal structures of both BVU_4064 and BF1687 proteins, solved at the JCSG center, show strikingly similar three-dimensional structures. The main difference between the two is that the two domains in the BVU_4064 protein are connected by a short linker, as opposed to a longer insertion made of 4 helices placed linearly along with a strand that is added to the C-terminal domain in the BF1687 protein. The N-terminal domain in both proteins, corresponding to the PF12985 (DUF3869) domain is a β-sandwich with pre-albumin-like fold, found in many proteins belonging to the Transthyretin clan of Pfam. The structures of C-terminal domains of both proteins, corresponding to the PF12986 (DUF3870) domain in BVU_4064 protein and an unclassified domain in the BF1687 protein, show significant structural similarity to bacterial pore-forming toxins. A helix in this domain is in an analogous position to a loop connecting the second and third strands in the toxin structures, where this loop is implicated to play a role in the toxin insertion into the host cell membrane. The same helix also points to the groove between the N- and C-terminal domains that are loosely held together by hydrophobic and hydrogen bond interactions. The presence of several conserved residues in this region together with these structural determinants could make it a functionally important region in these proteins.ConclusionsStructural analysis of BVU_4064 and BF1687 points to possible roles in mediating multiple interactions on the cell-surface/extracellular matrix. In particular the N-terminal domain could be involved in adhesive interactions, the C-terminal domain and the inter-domain groove in lipid or carbohydrate interactions

VIPERdb: a relational database for structural virology

VIPERdb () is a database for icosahedral virus capsid structures. Our aim is to provide a comprehensive resource specific to the needs of the structural virology community, with an emphasis on the description and comparison of derived data from structural and energetic analyses of capsids. A relational database implementation based on a schema for macromolecular structure makes the data highly accessible to the user, allowing detailed queries at the atomic level. Together with curation practices that maintain data uniformity, this will facilitate structural bioinformatics studies of virus capsids. User friendly search, visualization and educational tools on the website allow both structural and derived data to be examined easily and extensively. Links to relevant literature, sequence and taxonomy databases are provided for each entry

POSA: a user-driven, interactive multiple protein structure alignment server.

POSA (Partial Order Structure Alignment), available at http://posa.godziklab.org, is a server for multiple protein structure alignment introduced in 2005 (Ye,Y. and Godzik,A. (2005) Multiple flexible structure alignment using partial order graphs. Bioinformatics, 21, 2362-2369). It is free and open to all users, and there is no login requirement, albeit there is an option to register and store results in individual, password-protected directories. In the updated POSA server described here, we introduce two significant improvements. First is an interface allowing the user to provide additional information by defining segments that anchor the alignment in one or more input structures. This interface allows users to take advantage of their intuition and biological insights to improve the alignment and guide it toward a biologically relevant solution. The second improvement is an interactive visualization with options that allow the user to view all superposed structures in one window (a typical solution for visualizing results of multiple structure alignments) or view them individually in a series of synchronized windows with extensive, user-controlled visualization options. The user can rotate structure(s) in any of the windows and study similarities or differences between structures clearly visible in individual windows

New triquinane-based host molecules : binding with diamines

Synthesis of several shape-specific hosts through heteroaromatic annulation on cis,syn,cis-triquinanedione 1 and X-ray crystal structure determination of one of them, 4a, is reported. Preliminary results of complexation between cleft 5a and diamines are reported

From cages to wedges and clefts : design of some novel hosts based on cis, syn, cis-triquinane framework

Annulation of aromatic rings on the folded cis, syn, cis -triquinane backbone has led to the design of potential host systems 4 and 6 whose crystal structures have been determined

From cages to wedges and clefts : Design of some novel hosts based on Image , Image , Image -triquinane framework

Annulation of aromatic rings on the folded Image ,Image ,Image -triquinane backbone has led to the design of potential host systems Image and Image whose crystal structures have been determined

Refractive outcomes following silicone oil tamponade in vitreoretinal surgery

PURPOSE: To evaluate the factors influencing the refractive outcomes following silicone oil tamponade (SOT) and silicone oil removal (SOR) in different lens statuses post-vitreoretinal surgery. DESIGN: Retrospective analysis of three different lens statuses. MATERIALS AND METHODS: This was a descriptive study that included 150 eyes of 147 patients who had undergone pars plana vitrectomy with SOT and SOR between January 2017 and June 2021. Demographic profile, spherical equivalent refraction (SER), and its association with clinical features were evaluated with SOT and post-SOR. RESULTS: The mean (±standard deviation [SD]) age was 47 ± 17.8 years, including all three groups. SER was represented in diopters (D). The mean ± SD refraction with SOT in phakic, pseudophakic, and aphakic was 4.28 ± 2.59 D, 2.94 ± 2.58 D, and 3.98 ± 4.82 D. The mean SER post-SOR in phakic, pseudophakic, and aphakic was −2.72 ± 2.03 D, −1.12 ± 1.41 D, and 8.22 ± 3.70 D. The diagnosis of rhegmatogenous retinal detachment (RRD) among 96 eyes (64%) is the common indicator to perform vitreoretinal (VR) surgery. A minority of subjects were managed with retinal lasers before VR surgery (14%). The macula was attached in 100 eyes (67.6%), the belt buckle was done in 37 eyes (24.7%), and the silicone oil viscosity with 1000 centistoke was chosen in 129 eyes (86%). CONCLUSION: SOT was used as a tamponade in VR surgeries irrespective of lens status. The significant predictor for post-SOR refraction in phakic and aphakic is post-SOT refraction. In pseudophakic, gender and diagnosis of RRD are the predictors of SOR refraction

Shared and Compartment‐Specific Processes in Nucleus Pulposus and Annulus Fibrosus During Intervertebral Disc Degeneration

Abstract Elucidating how cell populations promote onset and progression of intervertebral disc degeneration (IDD) has the potential to enable more precise therapeutic targeting of cells and mechanisms. Single‐cell RNA‐sequencing (scRNA‐seq) is performed on surgically separated annulus fibrosus (AF) (19,978; 26,983 cells) and nucleus pulposus (NP) (20,884; 24,489 cells) from healthy and diseased human intervertebral discs (IVD). In both tissue types, depletion of cell subsets involved in maintenance of healthy IVD is observed, specifically the immature cell subsets – fibroblast progenitors and stem cells – indicative of an impairment of normal tissue self‐renewal. Tissue‐specific changes are also identified. In NP, several fibrotic populations are increased in degenerated IVD, indicating tissue‐remodeling. In degenerated AF, a novel disease‐associated subset is identified, which expresses disease‐promoting genes. It is associated with pathogenic biological processes and the main gene regulatory networks include thrombospondin signaling and FOXO1 transcription factor. In NP and AF cells thrombospondin protein promoted expression of genes associated with TGFβ/fibrosis signaling, angiogenesis, and nervous system development. The data reveal new insights of both shared and tissue‐specific changes in specific cell populations in AF and NP during IVD degeneration. These identified mechanisms and molecules are novel and more precise targets for IDD prevention and treatment

doi:10.1093/nar/gkj032 VIPERdb: a relational database for structural virology

VIPERd