A comprehensive analysis of non-sequential alignments between all protein structures

<p>Abstract</p> <p>Background</p> <p>The majority of relations between proteins can be represented as a conventional sequential alignment. Nevertheless, unusual non-sequential alignments with different connectivity of the aligned fragments in compared proteins have been reported by many researchers. It is interesting to understand those non-sequential alignments; are they unique, sporadic cases or they occur frequently; do they belong to a few specific folds or spread among many different folds, as a common feature of protein structure. We present here a comprehensive large-scale study of non-sequential alignments between available protein structures in Protein Data Bank.</p> <p>Results</p> <p>The study has been conducted on a non-redundant set of 8,865 protein structures aligned with the aid of the TOPOFIT method. It has been estimated that between 17.4% and 35.2% of all alignments are non-sequential depending on variations in the parameters. Analysis of the data revealed that non-sequential relations between proteins do occur systematically and in large quantities. Various sizes and numbers of non-sequential fragments have been observed with all possible complexities of fragment rearrangements found for alignments consisting of up to 12 fragments. It has been found that non-sequential alignments are not limited to proteins of any particular fold and are present in more than two hundred of them. Moreover, many of them are found between proteins with different fold assignments. It has been shown that protein structure symmetry does not explain non-sequential alignments. Therefore, compelling evidences have been provided that non-sequential alignments between proteins are systematic and widespread across the protein universe.</p> <p>Conclusion</p> <p>The phenomenon of the widespread occurrence of non-sequential alignments between proteins might represent a missing rule of protein structure organization. More detailed study of this phenomenon will enhance our understanding of protein stability, folding, and evolution.</p

TOPOFIT-DB, a database of protein structural alignments based on the TOPOFIT method

TOPOFIT-DB (T-DB) is a public web-based database of protein structural alignments based on the TOPOFIT method, providing a comprehensive resource for comparative analysis of protein structure families. The TOPOFIT method is based on the discovery of a saturation point on the alignment curve (topomax point) which presents an ability to objectively identify a border between common and variable parts in a protein structural family, providing additional insight into protein comparison and functional annotation. TOPOFIT also effectively detects non-sequential relations between protein structures. T-DB provides users with the convenient ability to retrieve and analyze structural neighbors for a protein; do one-to-all calculation of a user provided structure against the entire current PDB release with T-Server, and pair-wise comparison using the TOPOFIT method through the T-Pair web page. All outputs are reported in various web-based tables and graphics, with automated viewing of the structure-sequence alignments in the Friend software package for complete, detailed analysis. T-DB presents researchers with the opportunity for comprehensive studies of the variability in proteins and is publicly available at

An AP Endonuclease 1–DNA Polymerase β Complex: Theoretical Prediction of Interacting Surfaces

Abasic (AP) sites in DNA arise through both endogenous and exogenous mechanisms. Since AP sites can prevent replication and transcription, the cell contains systems for their identification and repair. AP endonuclease (APEX1) cleaves the phosphodiester backbone 5′ to the AP site. The cleavage, a key step in the base excision repair pathway, is followed by nucleotide insertion and removal of the downstream deoxyribose moiety, performed most often by DNA polymerase beta (pol-β). While yeast two-hybrid studies and electrophoretic mobility shift assays provide evidence for interaction of APEX1 and pol-β, the specifics remain obscure. We describe a theoretical study designed to predict detailed interacting surfaces between APEX1 and pol-β based on published co-crystal structures of each enzyme bound to DNA. Several potentially interacting complexes were identified by sliding the protein molecules along DNA: two with pol-β located downstream of APEX1 (3′ to the damaged site) and three with pol-β located upstream of APEX1 (5′ to the damaged site). Molecular dynamics (MD) simulations, ensuring geometrical complementarity of interfaces, enabled us to predict interacting residues and calculate binding energies, which in two cases were sufficient (∼−10.0 kcal/mol) to form a stable complex and in one case a weakly interacting complex. Analysis of interface behavior during MD simulation and visual inspection of interfaces allowed us to conclude that complexes with pol-β at the 3′-side of APEX1 are those most likely to occur in vivo. Additional multiple sequence analyses of APEX1 and pol-β in related organisms identified a set of correlated mutations of specific residues at the predicted interfaces. Based on these results, we propose that pol-β in the open or closed conformation interacts and makes a stable interface with APEX1 bound to a cleaved abasic site on the 3′ side. The method described here can be used for analysis in any DNA-metabolizing pathway where weak interactions are the principal mode of cross-talk among participants and co-crystal structures of the individual components are available

The First Post-Kepler Brightness Dips of KIC 8462852

We present a photometric detection of the first brightness dips of the unique variable star KIC 8462852 since the end of the Kepler space mission in 2013 May. Our regular photometric surveillance started in October 2015, and a sequence of dipping began in 2017 May continuing on through the end of 2017, when the star was no longer visible from Earth. We distinguish four main 1-2.5% dips, named "Elsie," "Celeste," "Skara Brae," and "Angkor", which persist on timescales from several days to weeks. Our main results so far are: (i) there are no apparent changes of the stellar spectrum or polarization during the dips; (ii) the multiband photometry of the dips shows differential reddening favoring non-grey extinction. Therefore, our data are inconsistent with dip models that invoke optically thick material, but rather they are in-line with predictions for an occulter consisting primarily of ordinary dust, where much of the material must be optically thin with a size scale <<1um, and may also be consistent with models invoking variations intrinsic to the stellar photosphere. Notably, our data do not place constraints on the color of the longer-term "secular" dimming, which may be caused by independent processes, or probe different regimes of a single process

A comprehensive analysis of non-sequential alignments between all protein structures-9

<p><b>Copyright information:</b></p><p>Taken from "A comprehensive analysis of non-sequential alignments between all protein structures"</p><p>http://www.biomedcentral.com/1472-6807/7/78</p><p>BMC Structural Biology 2007;7():78-78.</p><p>Published online 16 Nov 2007</p><p>PMCID:PMC2213659.</p><p></p>r of fragments in the alignment. Bar charts on the top and on the right of the picture reflect the occurrence of alignments with a particular number of fragments and number of rearrangements. Only alignments with more that one fragment rearrangement have been considered to calculate the bar proportion. The numbers on the bars help visualize the scale. The area in the right-upper corner is not populated because of a lack of statistics (see text)

A comprehensive analysis of non-sequential alignments between all protein structures-1

<p><b>Copyright information:</b></p><p>Taken from "A comprehensive analysis of non-sequential alignments between all protein structures"</p><p>http://www.biomedcentral.com/1472-6807/7/78</p><p>BMC Structural Biology 2007;7():78-78.</p><p>Published online 16 Nov 2007</p><p>PMCID:PMC2213659.</p><p></p>) and C2-domain of synaptotagmin I (PDB-code , shown on b) have been aligned by TOPOFIT with the of 108/1.2 Å. The alignment consists of two segments colored in blue and green. The green segment represents a -strand and is located at N-terminal in synaptotagmin and at C-terminal in phospholipase. Thus the alignment is the circular permutation. c) displays the circular diagram of the alignment. d) displays the alignment plot corresponding to the alignment

A comprehensive analysis of non-sequential alignments between all protein structures-3

<p><b>Copyright information:</b></p><p>Taken from "A comprehensive analysis of non-sequential alignments between all protein structures"</p><p>http://www.biomedcentral.com/1472-6807/7/78</p><p>BMC Structural Biology 2007;7():78-78.</p><p>Published online 16 Nov 2007</p><p>PMCID:PMC2213659.</p><p></p>PDB-code :A) have been aligned by TOPOFIT with of 115/1.7 Å. The longest sequential alignment is colored in blue. The fragment aligned in reverse order is colored in orange. The right side of the picture displays the corresponding alignment plot