No abstract

The physical and chemical properties of domain-domain interactions have been analysed in two-domain proteins selected from the protein classification, CATH. The two-domain structures were divided into those derived from (i) monomeric proteins, or (ii) oligomeric or complexed proteins. The size, polarity, hydrogen bonding and packing of the intra-chain domain interface were calculated for both sets of two-domain structures. The results were compared with inter-chain interface parameters from permanent and non-obligate protein-protein complexes. In general, the intra-chain domain and inter-chain interfaces were remarkably similar. Many of the intra-chain interface properties are intermediate between those calculated for permanent and non-obligate inter-chain complexes. Residue interface propensities were also found to be very similar, with hydrophobic residues playing a major role, together with positively charged arginine residues. In addition, the residue composition of the domain interfaces were found to be more comparable with domain surfaces than domain cores. The implications of these results for domain swapping and protein folding are discussed.

This paper studies strategies for collision avoidance between two persons walking along crossing trajectories. It has been previously demonstrated that walkers are able to anticipate the risk of future collision and to react accordingly. The avoidance task has been described as a mutual control of the future distance of closest approach, MPD (i.e., Mininum Predicted Distance). In this paper, we studied the role of each walker in the task of controlling MPD. A specific question was: does the walker giving way (2nd at the crossing) and the one passing first set similar and coordinated strategies? To answer this question, we inspected the effect of motion adaptations on the future distance of closest approach. This analysis is relevant in the case of collision avoidance because subtle anticipatory behaviors or large last moment adaptations can finally yield the same result upon the final crossing distance. Results showed that collision avoidance is performed collaboratively and the crossing order impacts both the contribution and the strategies used: the participant giving way contributes more than the one passing first to avoid the collision. Both walkers reorient their path but the participant giving way also adapts his speed. Future work is planned to investigate the influence of crossing angle and TTC on adaptations as well as new types of interactions, such as intercepting or meeting tasks.

BackgroundA number of methods are now available to perform automatic assignment of periodic secondary structures from atomic coordinates, based on different characteristics of the secondary structures. In general these methods exhibit a broad consensus as to the location of most helix and strand core segments in protein structures. However the termini of the segments are often ill-defined and it is difficult to decide unambiguously which residues at the edge of the segments have to be included. In addition, there is a "twilight zone" where secondary structure segments depart significantly from the idealized models of Pauling and Corey. For these segments, one has to decide whether the observed structural variations are merely distorsions or whether they constitute a break in the secondary structure.MethodsTo address these problems, we have developed a method for secondary structure assignment, called KAKSI. Assignments made by KAKSI are compared with assignments given by DSSP, STRIDE, XTLSSTR, PSEA and SECSTR, as well as secondary structures found in PDB files, on 4 datasets (X-ray structures with different resolution range, NMR structures).ResultsA detailed comparison of KAKSI assignments with those of STRIDE and PSEA reveals that KAKSI assigns slightly longer helices and strands than STRIDE in case of one-to-one correspondence between the segments. However, KAKSI tends also to favor the assignment of several short helices when STRIDE and PSEA assign longer, kinked, helices. Helices assigned by KAKSI have geometrical characteristics close to those described in the PDB. They are more linear than helices assigned by other methods. The same tendency to split long segments is observed for strands, although less systematically. We present a number of cases of secondary structure assignments that illustrate this behavior.ConclusionOur method provides valuable assignments which favor the regularity of secondary structure segments.

To assess the reliability of fold assignments to protein sequences, we developed a fold recognition method called FROST (Fold Recognition-Oriented Search Tool) based on a series of filters and a database specifically designed as a benchmark for this new method under realistic conditions. This benchmark database consists of proteins for which there exists, at least, another protein with an extensively similar 3D structure in a database of representative 3D structures (i.e., more than 65% of the residues in both proteins can be structurally aligned). Because the testing of our method must be carried out under conditions similar to those of real fold recognition experiments, no protein pair with sequence similarity detectable using standard sequence comparison methods such as FASTA is included in the benchmark database. While using FROST, we achieved a coverage of 60% for a rate of error of 1%. To obtain a baseline for our method, we used PSI-BLAST and 3D-PSSM. Under the same conditions, for a 1% error rate, coverages for PSI-BLAST and 3D-PSSM were 33 and 56%, respectively.

The Rel/NF-kB family of transcription factors controls the expression of a wide variety of genes that are implicated in immune and in¯ammatory responses and cellular proliferation. Disregulation of NF-kB is associated with cellular transformation and the maintenance of a high anti-apoptotic threshold in transformed cells. NF-kB activity is in turn regulated by its sequestration in the cytoplasm by the inhibitor IkB. IkBa, the most abundant and well-characterized member of the IkB multiprotein family, is rapidly degraded in response to multiple physiologic stimuli. In the present study we show that not only the amino-terminus, but also the carboxy-terminus of IkBa contain transferable signals that must be simultaneously present in an unrelated protein to render it susceptible to activation-induced, proteasome-mediated degradation. We show here that IkBa amino-terminal modi®cations occur independently of the carboxy-terminus. Moreover, we present evidence indicating a critical role for the carboxy-terminal region in facilitating proteolysis by the catalytic core of the proteasome. When incubated with 20S proteasome extracted from rat liver, IkBa was quickly degraded while a deletion mutant lacking the carboxy-terminus was resistant to proteolysis. Likewise, chimeric proteins of beta-galactosidase with the IkBa carboxy-terminus were degraded in vitro independently of the presence of the IkBa amino-terminus, whereas chimeric proteins lacking the IkBa carboxy-terminus were stable. Our results identify the carboxy-terminus of IkBa as a domain critical for degradation through interaction with an as yet unidenti®ed component of the proteasome.

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Background: Recent approaches for predicting the three-dimensional (3D) structure of proteins such as de novo or fold recognition methods mostly rely on simplified energy potential functions and a reduced representation of the polypeptide chain. These simplifications facilitate the exploration of the protein conformational space but do not permit to capture entirely the subtle relationship that exists between the amino acid sequence and its native structure. It has been proposed that physics-based energy functions together with techniques for sampling the conformational space, e.g., Monte Carlo or molecular dynamics (MD) simulations, are better suited to the task of modelling proteins at higher resolutions than those of models obtained with the former type of methods. In this study we monitor different protein structural properties along MD trajectories to discriminate correct from erroneous models. These models are based on the sequence-structure alignments provided by our fold recognition method, FROST. We define correct models as being built from alignments of sequences with structures similar to their native structures and erroneous models from alignments of sequences with structures unrelated to their native structures.