Comparison of protein interaction networks reveals species conservation and divergence

BACKGROUND: Recent progresses in high-throughput proteomics have provided us with a first chance to characterize protein interaction networks (PINs), but also raised new challenges in interpreting the accumulating data. RESULTS: Motivated by the need of analyzing and interpreting the fast-growing data in the field of proteomics, we propose a comparative strategy to carry out global analysis of PINs. We compare two PINs by combining interaction topology and sequence similarity to identify conserved network substructures (CoNSs). Using this approach we perform twenty-one pairwise comparisons among the seven recently available PINs of E.coli, H.pylori, S.cerevisiae, C.elegans, D.melanogaster, M.musculus and H.sapiens. In spite of the incompleteness of data, PIN comparison discloses species conservation at the network level and the identified CoNSs are also functionally conserved and involve in basic cellular functions. We investigate the yeast CoNSs and find that many of them correspond to known complexes. We also find that different species harbor many conserved interaction regions that are topologically identical and these regions can constitute larger interaction regions that are topologically different but similar in framework. Based on the species-to-species difference in CoNSs, we infer potential species divergence. It seems that different species organize orthologs in similar but not necessarily the same topology to achieve similar or the same function. This attributes much to duplication and divergence of genes and their associated interactions. Finally, as the application of CoNSs, we predict 101 protein-protein interactions (PPIs), annotate 339 new protein functions and deduce 170 pairs of orthologs. CONCLUSION: Our result demonstrates that the cross-species comparison strategy we adopt is powerful for the exploration of biological problems from the perspective of networks

Quantitative investigation of two metallohydrolases by X-ray absorption spectroscopy near-edge spectroscopy

The last several years have witnessed a tremendous increase in biological applications using X-ray absorption spectroscopy (BioXAS), thanks to continuous advancements in synchrotron radiation (SR) sources and detector technology. However, XAS applications in many biological systems have been limited by the intrinsic limitations of the Extended X-ray Absorption Fine Structure (EXAFS) technique e.g., the lack of sensitivity to bond angles. As a consequence, the application of the X-ray absorption near-edge structure (XANES) spectroscopy changed this scenario that is now continuously changing with the introduction of the first quantitative XANES packages such as Minut XANES (MXAN). Here we present and discuss the XANES code MXAN, a novel XANES-fitting package that allows a quantitative analysis of experimental data applied to Zn K-edge spectra of two metalloproteins: Leptospira interrogans Peptide deformylase (LiPDF) and acutolysin-C, a representative of snake venom metalloproteinases (SVMPs) from Agkistrodon acutus venom. The analysis on these two metallohydrolases reveals that proteolytic activities are correlated to subtle conformation changes around the zinc ion. In particular, this quantitative study clarifies the occurrence of the LiPDF catalytic mechanism via a two-water-molecules model, whereas in the acutolysin-C we have observed a different proteolytic activity correlated to structural changes around the zinc ion induced by pH variations

BIOINFORMATICS APPLICATIONS NOTE Systems biology

NetAlign: a web-based tool for comparison o

Crystal Structure of Uroporphyrinogen Decarboxylase from Bacillus subtilis

Uroporphyrinogen decarboxylase (UROD) is a branch point enzyme in the biosynthesis of the tetrapyrroles. It catalyzes the decarboxylation of four acetate groups of uroporphyrinogen III to yield coproporphyrinogen III, leading to heme and chlorophyll biosynthesis. UROD is a special type of nonoxidative decarboxylase, since no cofactor is essential for catalysis. In this work, the first crystal structure of a bacterial UROD, Bacillus subtilis UROD (UROD(Bs)), has been determined at a 2.3 Å resolution. The biological unit of UROD(Bs) was determined by dynamic light scattering measurements to be a homodimer in solution. There are four molecules in the crystallographic asymmetric unit, corresponding to two homodimers. Structural comparison of UROD(Bs) with eukaryotic URODs reveals a variation of two loops, which possibly affect the binding of substrates and release of products. Structural comparison with the human UROD-coproporphyrinogen III complex discloses a similar active cleft, with five invariant polar residues (Arg29, Arg33, Asp78, Tyr154, and His322) and three invariant hydrophobic residues (Ile79, Phe144, and Phe207), in UROD(Bs). Among them, Asp78 may interact with the pyrrole NH groups of the substrate, and Arg29 is a candidate for positioning the acetate groups of the substrate. Both residues may also play catalytic roles

Coevolution is a short-distance force at the protein interaction level and correlates with the modular organization of protein networks

AbstractWe investigated what roles coevolution plays in shaping yeast protein interaction network (PIN). We found that the extent of coevolution between two proteins decreases rapidly as their interacting distance on the PIN increases, suggesting coevolutionary constraint is a short-distance force at the molecular level. We also found that protein–protein interactions (PPIs) with strong coevolution tend to be enriched in interconnected clusters, whereas PPIs with weak coevolution are more frequently present at inter-cluster region. The findings indicate the close relationship between coevolution and modular organization of PINs, and may provide insights into evolution and modularity of cellular networks

Purification, crystallization and preliminary X-ray diffraction analysis of saxthrombin, a thrombin-like enzyme from Gloydius saxatilis venom

The thrombin-like enzyme saxthrombin has been purified from G. saxatilis snake venom. Crystallization conditions were found and a data set was obtained to 1.43 Å

Crystallization and preliminary X-ray crystallographic analysis of agkicetin-C from Deinagkistrodon acutus venom

The crystallization and preliminary crystallographic analysis of agkicetin-C, a well known platelet glycoprotein Ib (GPIb) antagonist from the venom of Deinagkistrodon acutus found in Anhui Province, China is reported

Structural Insights into Mouse H-FABP

Intracellular fatty acid-binding proteins are evolutionarily highly conserved proteins. The major functions and responsibilities of this family are the regulation of FA uptake and intracellular transport. The structure of the H-FABP ortholog from mouse (Mus musculus) had not been revealed at the time this study was completed. Thus, further exploration of the structural properties of mouse H-FABP is expected to extend our knowledge of the model animal’s molecular mechanism of H-FABP function. Here, we report the high-resolution crystal structure and the NMR characterization of mouse H-FABP. Our work discloses the unique structural features of mouse H-FABP, offering a structural basis for the further development of small-molecule inhibitors for H-FABP