Identification Of Related Proteins Research Articles

Haspin-like proteins: a new family of evolutionarily conserved putative eukaryotic protein kinases.

Haspin (haploid germ cell-specific nuclear protein kinase) is reported to be a serine/threonine kinase that may play a role in cell-cycle cessation and differentiation of haploid germ cells. In addition, Haspin mRNA can be detected in diploid cell lines and tissues. Here, Haspin-like proteins are identified in several major eukaryotic phyla-including yeasts, plants, flies, fish, and mammals-and an extended group in Caenorhabditis elegans. The Haspin-like proteins have a complete but divergent eukaryotic protein kinase domain sequence. Although clearly related to one another and to other eukaryotic protein kinases, the Haspin-related proteins lack conservation of a subset of residues that are almost invariant in known kinases and possess distinctive inserted regions. In fact, phylogenetic analysis indicates that the Haspin-like proteins form a novel eukaryotic protein kinase family distinct from those previously defined. The identification of related proteins in model organisms provides some initial insight into their functional properties and will provide new experimental avenues by which to determine the function of the Haspin proteins in mammalian cells.

Identification of related proteins with weak sequence identity using secondary structure information.

Molecular modeling of proteins is confronted with the problem of finding homologous proteins, especially when few identities remain after the process of molecular evolution. Using even the most recent methods based on sequence identity detection, structural relationships are still difficult to establish with high reliability. As protein structures are more conserved than sequences, we investigated the possibility of using protein secondary structure comparison (observed or predicted structures) to discriminate between related and unrelated proteins sequences in the range of 10%-30% sequence identity. Pairwise comparison of secondary structures have been measured using the structural overlap (Sov) parameter. In this article, we show that if the secondary structures likeness is >50%, most of the pairs are structurally related. Taking into account the secondary structures of proteins that have been detected by BLAST, FASTA, or SSEARCH in the noisy region (with high E: value), we show that distantly related protein sequences (even with <20% identity) can be still identified. This strategy can be used to identify three-dimensional templates in homology modeling by finding unexpected related proteins and to select proteins for experimental investigation in a structural genomic approach, as well as for genome annotation.

Identification of related proteins on family, superfamily and fold level

Proteins might have considerable structural similarities even when no evolutionary relationship of their sequences can be detected. This property is often referred to as the proteins sharing only a “fold”. Of course, there are also sequences of common origin in each fold, called a “superfamily”, and in them groups of sequences with clear similarities, designated “family”. Developing algorithms to reliably identify proteins related at any level is one of the most important challenges in the fast growing field of bioinformatics today. However, it is not at all certain that a method proficient at finding sequence similarities performs well at the other levels, or vice versa.Here, we have compared the performance of various search methods on these different levels of similarity. As expected, we show that it becomes much harder to detect proteins as their sequences diverge. For family related sequences the best method gets 75 % of the top hits correct. When the sequences differ but the proteins belong to the same superfamily this drops to 29 %, and in the case of proteins with only fold similarity it is as low as 15 %. We have made a more complete analysis of the performance of different algorithms than earlier studies, also including threading methods in the comparison. Using this method a more detailed picture emerges, showing multiple sequence information to improve detection on the two closer levels of relationship. We have also compared the different methods of including this information in prediction algorithms.For lower specificities, the best scheme to use is a linking method connecting proteins through an intermediate hit. For higher specificities, better performance is obtained by PSI-BLAST and some procedures using hidden Markov models. We also show that a threading method, THREADER, performs significantly better than any other method at fold recognition.

Purification of tropomyosin from Saccharomyces cerevisiae and identification of related proteins in Schizosaccharomyces and Physarum.

Tropomyosin is a key component of the contractile systems found in muscle and nonmuscle cells of higher eukaryotes. Based on properties common to all tropomyosins, we have purified a protein from Saccharomyces cerevisiae that resembles tropomyosins from higher cells. The yeast protein remains soluble after heat treatment at 90 degrees C, has an apparent polypeptide molecular weight of 33,000, an isoelectric point of 4.5, a Stokes radius of 3.5 nm, and a sedimentation coefficient of 2.6 S. It binds F-actin in a Mg2+-dependent, KCl-modulated manner, up to a stoichiometry of about 1 polypeptide per 3.0 actin monomers. In all these properties it is very similar to tropomyosins from higher cells. Antigen-affinity-purified antibodies specifically recognize the Mr 33,000 polypeptide among total yeast proteins and crossreact with bovine brain tropomyosin. In addition, the antibodies specifically crossreact with heat-stable Mr 33,000 polypeptides in extracts of Schizosaccharomyces pombe and Physarum polycephalum. Our detection of tropomyosin in lower eukaryotes suggests that they might have contractile systems very similar to those found in higher organisms.