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S A Teichmann

Publications and source records attributed to S A Teichmann.

11 recordsLinked to original sources
PubMed2000

Immunoglobulin superfamily proteins in Caenorhabditis elegans.

The predicted proteins of the genome of Caenorhabditis elegans were analysed by various sequence comparison methods to identify the repertoire of proteins that are members of the immunoglobulin superfamily (IgSF). The IgSF is one of the largest families of protein domain in this genome and likely to be one of the major families in other multicellular eukaryotes too. This is because members of the superfamily are involved in a variety of functions including cell-cell recognition, cell-surface receptors, muscle structure and, in higher organisms, the immune system. Sixty-four proteins with 488 I set IgSF domains were identified largely by using Hidden Markov models. The domain architectures of the protein products of these 64 genes are described. Twenty-one of these had been characterised previously. We show that another 25 are related to proteins of known function. The C. elegans IgSF proteins can be classified into five broad categories: muscle proteins, protein kinases and phosphatases, three categories of proteins involved in the development of the nervous system, leucine-rich repeat containing proteins and proteins without homologues of known function, of which there are 18. The 19 proteins involved in nervous system development that are not kinases or phosphatases are homologues of neuroglian, axonin, NCAM, wrapper, klingon, ICCR and nephrin or belong to the recently identified zig gene family. Out of the set of 64 genes, 22 are on the X chromosome. This study should be seen as an initial description of the IgSF repertoire in C. elegans, because the current gene definitions may contain a number of errors, especially in the case of long sequences, and there may be IgSF genes that have not yet been detected. However, the proteins described here do provide an overview of the bulk of the repertoire of immunoglobulin superfamily members in C. elegans, a framework for refinement and extension of the repertoire as gene and protein definitions improve, and the basis for investigations of their function and for comparisons with the repertoires of other organisms.

Animals↗
PubMed2000

Fast assignment of protein structures to sequences using the intermediate sequence library PDB-ISL.

MOTIVATION: For large-scale structural assignment to sequences, as in computational structural genomics, a fast yet sensitive sequence search procedure is essential. A new approach using intermediate sequences was tested as a shortcut to iterative multiple sequence search methods such as PSI-BLAST. RESULTS: A library containing potential intermediate sequences for proteins of known structure (PDB-ISL) was constructed. The sequences in the library were collected from a large sequence database using the sequences of the domains of proteins of known structure as the query sequences and the program PSI-BLAST. Sequences of proteins of unknown structure can be matched to distantly related proteins of known structure by using pairwise sequence comparison methods to find homologues in PDB-ISL. Searches of PDB-ISL were calibrated, and the number of correct matches found at a given error rate was the same as that found by PSI-BLAST. The advantage of this library is that it uses pairwise sequence comparison methods, such as FASTA or BLAST2, and can, therefore, be searched easily and, in many cases, much more quickly than an iterative multiple sequence comparison method. The procedure is roughly 20 times faster than PSI-BLAST for small genomes and several hundred times for large genomes. AVAILABILITY: Sequences can be submitted to the PDB-ISL servers at http://stash.mrc-lmb.cam.ac.uk/PDB_ISL/ or http://cyrah.ebi.ac.uk:1111/Serv/PDB_ISL/ and can be downloaded from ftp://ftp.ebi.ac.uk/pub/contrib/jong/PDB_+ ++ISL/ CONTACT: sat@mrc-lmb.cam.ac.uk and jong@ebi.ac.uk

Peptide Library↗
PubMed1999

Is there a phylogenetic signal in prokaryote proteins?

Using the sequence information from nine completely sequenced bacterial genomes, we extract 32 protein families that are thought to contain orthologous proteins from each genome. The alignments of these 32 families are used to construct a phylogeny with the neighbor-joining algorithm. This tree has several topological features that are different from the conventional phylogeny, yet it is highly reliable according to its bootstrap values. Upon closer study of the individual families used, it is clear that the strong phylogenetic signal comes from three families, at least two of which are good candidates for horizontal transfer. The tree from the remaining 29 families consists almost entirely of noise at the level of bacterial phylum divisions, indicating that, even with large amounts of data, it may not be possible to reconstruct the prokaryote phylogeny using standard sequence-based methods.

Arginine-tRNA Ligase↗
PubMed1999

Telomerases.

Telomerases are RNA-dependent polymerases that catalyse the synthesis of the telomeric DNA at the tips of eukaryotic chromosomes. The recent identification of the catalytic subunit of telomerases from several different species suggests that the core of the telomerase is conserved. The proposed sequence and structural homology between the telomerase catalytic subunit and reverse transcriptases, together with a wealth of genetic and biochemical information, has led to significant advances in our understanding of the mechanism by which telomerases synthesise telomeric DNA.

Amino Acid Sequence↗
PubMed1999

Advances in structural genomics.

New computational techniques have allowed protein folds to be assigned to all or parts of between a quarter (Caenorhabditis elegans) and a half (Mycoplasma genitalium) of the individual protein sequences in different genomes. These assignments give a new perspective on domain structures, gene duplications, protein families and protein folds in genome sequences.

Animals↗
PubMed1998

Structural assignments to the Mycoplasma genitalium proteins show extensive gene duplications and domain rearrangements.

The parasitic bacterium Mycoplasma genitalium has a small, reduced genome with close to a basic set of genes. As a first step toward determining the families of protein domains that form the products of these genes, we have used the multiple sequence programs PSI-BLAST and GEANFAMMER to match the sequences of the 467 gene products of M. genitalium to the sequences of the domains that form proteins of known structure [Protein Data Bank (PDB) sequences]. PDB sequences (274) match all of 106 M. genitalium sequences and some parts of another 85; thus, 41% of its total sequences are matched in all or part. The evolutionary relationships of the PDB domains that match M. genitalium are described in the structural classification of proteins (SCOP) database. Using this information, we show that the domains in the matched M. genitalium sequences come from 114 superfamilies and that 58% of them have arisen by gene duplication. This level of duplication is more than twice that found by using pairwise sequence comparisons. The PDB domain matches also describe the domain structure of the matched sequences: just over a quarter contain one domain and the rest have combinations of two or more domains.

Bacterial Proteins↗
PubMed1998

Structure and distribution of pentapeptide repeats in bacteria.

We report the discovery of a novel family of proteins, each member contains tandem pentapeptide (five residue) repeats, described by the motif A(D/N)LXX. Members of this family are both membrane bound and cytoplasmic. The function of these repeats is uncertain, but they may have a targeting or structural function rather than enzymatic activity. This family is most common in cyanobacteria, suggesting a function related to cyanobacterial-specific metabolism. Although no experimental information is available for the structure of this family, it is predicted that the tandem pentapeptide repeats will form a right-handed beta-helical structure. A structural model of the pentapeptide repeats is presented.

Amino Acid Sequence↗
PubMed1998

DIVCLUS: an automatic method in the GEANFAMMER package that finds homologous domains in single- and multi-domain proteins.

MOTIVATION: Large-scale determination of relationships between the proteins produced by genome sequences is now common. All protein sequences are matched and those that have high match scores are clustered into families. In cases where the proteins are built of several domains or duplication modules, this can lead to misleading results. Consider the very simple example of three proteins: 1, formed by duplication modules A and B; 2, formed by duplication modules B' and C; and 3, formed by duplication modules C' and D. Duplication modules B and B' are homologous, as are C and C'. Matching the sequences of 1, 2 and 3 followed by simple single-linkage clustering would put all three in the same family, even though proteins 1 and 3 are not related. This is because the different parts of 2 match 1 and 3. This paper describes a procedure, DIVCLUS, that divides such complex clusters of partially related sequences into simple clusters that contain only related duplication modules. In the example just given, it would produce two groups of sequences: the first with domains B of sequence 1 and B of sequence 2, and the second with domain C of sequence 2 and C of sequence 3. DIVCLUS is part of a package called GEANFAMMER, for GEnome ANalysis and protein FAMily MakER. The package automates the detection of families of duplication modules from a protein sequence database. RESULTS: DIVCLUS has been applied to the division of single-linkage clusters generated from the protein sequences of six completely sequenced bacterial genomes. Out of 12 013 genes in these six genomes, 4563 single- and multi-domain sequences formed 1071 complex clusters. Application of the DIVCLUS program resolved these clusters into 2113 clusters corresponding to single duplication modules. AVAILABILITY: The perl5 program and its documentation are available at the following address: http://www.mrc-lmb.cam.ac.uk/genomes/ and by anonymous ftp at ftp.mrc-lmb.cam.ac.uk in the directory /pub/genomes/Software/. CONTACT: sat@mrc-lmb.cam.ac.uk; jong@mrc-lmb. cam.ac.uk

Algorithms↗
PubMed1997

Intermediate sequences increase the detection of homology between sequences.

Two homologous sequences, which have diverged beyond the point where their homology can be recognised by a simple direct comparison, can be related through a third sequence that is suitably intermediate between the two. High scores, for a sequence match between the first and third sequences and between the second and the third sequences, imply that the first and second sequences are related even though their own match score is low. We have tested the usefulness of this idea using a database that contains the sequences of 971 protein domains whose structures are known and whose residue identities with each other are some 40% or less (PDB40D). On the basis of sequence and structural information, 2143 pairs of these sequences are known to have an evolutionary relationship. FASTA, in an all-against-all comparison of the sequences in the database, detected 320 (15%) of these relationships as well as three false positive (i.e. 1% error rate). Using intermediate sequences found by FASTA matches of PDB40D sequences to those in the large non-redundant OWL database we could detect 550 evolutionary relationships with an error rate of 1%. This means the intermediate sequence procedure increases the ability to recognise the evolutionary relationships amongst the PDB40D sequences by 70%.

Amino Acid Sequence↗