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J C Rayner

Publications and source records attributed to J C Rayner.

14 recordsLinked to original sources
PubMed2002

Extensive polymorphism in the plasmodium vivax merozoite surface coat protein MSP-3alpha is limited to specific domains.

Plasmodium merozoites are covered by a complex coat of surface proteins. Several of the Merozoite Surface Proteins (MSPs) that make up this coat have been proposed as vaccine candidates although some of the MSPs are known to be highly polymorphic. We present here the first survey and analysis of the polymorphism in the recently characterized P. vivax surface protein PvMSP-3alpha. Full length or partial sequences were obtained for the Pvmsp-3alpha gene from isolates originating in Central and South America, Asia and the Pacific. The Pvmsp-3alpha sequence is remarkably diverse, but this extensive diversity is largely restricted to certain domains of the encoded protein. An acidic C-terminal domain and a smaller hydrophilic N-terminus are relatively conserved, while a central domain containing coiled-coil heptad repeats is highly polymorphic and in some isolates of P. vivax is partially deleted. Unlike other MSPs, there is no evidence of allelic families of PvMSP-3alpha gene sequences, and no evidence that certain patterns of polymorphism group within isolates of similar geographical origin. The distribution and nature of polymorphism suggest that there are functional restrictions on mutations in this gene, and have implications for inclusion of PvMSP-3alpha as a candidate in a P. vivax vaccine.

Amino Acid Sequence↗
PubMed2001

A Plasmodium falciparum homologue of Plasmodium vivax reticulocyte binding protein (PvRBP1) defines a trypsin-resistant erythrocyte invasion pathway.

Invasion of erythrocytes by Plasmodium merozoites is an intricate process involving multiple receptor-ligand interactions. The glycophorins and an unknown trypsin sensitive factor are all erythrocyte receptors used during invasion by the major human pathogen Plasmodium falciparum. However, only one erythrocyte receptor, Glycophorin A, has a well-established cognate parasite ligand, the merozoite protein erythrocyte binding antigen-175 (EBA-175). The involvement of several other parasite proteins during invasion have been proposed, but no direct evidence links them with a specific invasion pathway. Here we report the identification and characterization of P. falciparum normocyte binding protein 1 (PfNBP1), an ortholog of Plasmodium vivax reticulocyte binding protein-1. PfNBP1 binds to a sialic acid dependent trypsin-resistant receptor on the erythrocyte surface that appears to be distinct from known invasion receptors. Antibodies against PfNBP1 can inhibit invasion of trypsinized erythrocytes and two P. falciparum strains that express truncated PfNBP1 are unable to invade trypsinized erythrocytes. One of these strain, 7G8, also does not invade Glycophorin B-negative erythrocytes. PfNBP1 therefore defines a novel trypsin-resistant invasion pathway and adds a level of complexity to current models for P. falciparum erythrocyte invasion.

Animals↗
PubMed2000

Two Plasmodium falciparum genes express merozoite proteins that are related to Plasmodium vivax and Plasmodium yoelii adhesive proteins involved in host cell selection and invasion.

Two related Plasmodium falciparum genes and their encoded proteins have been identified by comparative analyses with Plasmodium vivax reticulocyte binding protein 2 (PvRBP-2). The P. falciparum genes have a structure which suggests that they may be the result of an evolutionary duplication event, as they share more than 8 kb of closely related nucleotide sequence but then have quite divergent unique 3' ends. Between these shared and unique regions is a complex set of repeats, the nature and number of which differs between the two genes, as well as between different P. falciparum strains. Both genes encode large hydrophilic proteins, which are concentrated at the invasive apical end of the merozoite and are predicted to be more than 350 kDa, with an N-terminal signal sequence and a single transmembrane domain near their C termini. Importantly, they also share gene structure and amino acid homology with the Plasmodium yoelii 235-kDa rhoptry protein family, which is also related to PvRBP-2. Together these Plasmodium proteins define an extended family of proteins that appear to function in erythrocyte selection and invasion. As such, they may prove to be essential components of malaria vaccine preparations.

Amino Acid Motifs↗
PubMed1999

The Saccharomyces cerevisiae protein Mnn10p/Bed1p is a subunit of a Golgi mannosyltransferase complex.

In the yeast Saccharomyces cerevisiae many of the N-linked glycans on cell wall and periplasmic proteins are modified by the addition of mannan, a large mannose-containing polysaccharide. Mannan comprises a backbone of approximately 50 alpha-1,6-linked mannoses to which are attached many branches consisting of alpha-1,2-linked and alpha-1,3-linked mannoses. The initiation and subsequent elongation of the mannan backbone is performed by two complexes of proteins in the cis Golgi. In this study we show that the product of the MNN10/BED1 gene is a component of one of these complexes, that which elongates the backbone. Analysis of interactions between the proteins in this complex shows that Mnn10p, and four previously characterized proteins (Anp1p, Mnn9p, Mnn11p, and Hoc1p) are indeed all components of the same large structure. Deletion of either Mnn10p, or its homologue Mnn11p, results in defects in mannan synthesis in vivo, and analysis of the enzymatic activity of the complexes isolated from mutant strains suggests that Mnn10p and Mnn11p are responsible for the majority of the alpha-1, 6-polymerizing activity of the complex.

Enzyme Activation↗
PubMed1999

Modelling ties in the sign test.

If ties occur in the sign test, the procedure recommended by Coakley and Heise (1996, Biometrics 52, 1242-1251) is the asymptotic uniformly most powerful nonrandomised test due to Putter (1955, Annals of Mathematical Statistics 26, 368-386). It may be shown that this is a consequence of how the probability of a tie is modelled. Other models with different optimal procedures can be constructed.

Biometry↗
PubMed1998

Identification of the MNN2 and MNN5 mannosyltransferases required for forming and extending the mannose branches of the outer chain mannans of Saccharomyces cerevisiae.

The mannan structure found on the N-linked glycans of the yeast Saccharomyces cerevisiae is composed of a long backbone of alpha-1, 6-linked mannose to which are attached branches consisting of two alpha-1,2-linked mannoses followed by an alpha-1,3-linked mannose. In the mutants mnn2 and mnn5, the addition of the first and second of these two mannoses, respectively, is defective. In this paper, we report the identification of the genes corresponding to these mutations. The two genes encode closely related proteins with distant homology to the known Mnn1p alpha-1,3-mannosyltransferase. We show that these proteins are localized in an early compartment of the yeast Golgi and that they are not physically associated with each other or with the two protein complexes known to be involved in synthesizing the alpha-1,6-linked backbone. The identification of Mnn2p and Mnn5p allows us to assign Golgi proteins to all of the catalytic steps in S. cerevisiae mannan synthesis.

Amino Acid Sequence↗
PubMed1997

A novel SNARE complex implicated in vesicle fusion with the endoplasmic reticulum.

Intracellular vesicular traffic is controlled in part by v- and t-SNAREs, integral membrane proteins which allow specific interaction and fusion between vesicles (v-SNAREs) and their target membranes (t-SNAREs). In yeast, retrograde transport from the Golgi complex to the ER is mediated by the ER t-SNARE Ufe1p, and also requires two other ER proteins, Sec20p and Tip20p, which bind each other. Although Sec20p is not a typical SNARE, we show that both it and Tip20p can be co-precipitated with Ufe1p, and that a growth-inhibiting mutation in Ufe1p can be compensated by a mutation in Sec20p. Furthermore, Sec22p, a v-SNARE implicated in forward transport from ER to Golgi, co-precipitates with Ufe1p and Sec20p, and SEC22 acts as an allele-specific multicopy suppressor of a temperature-sensitive ufe1 mutation. These results define a new functional SNARE complex, with features distinct from the plasma membrane and cis-Golgi complexes previously identified. They also show that a single v-SNARE can be involved in both anterograde and retrograde transport, which suggests that the mere presence of a particular v-SNARE may not be sufficient to determine the preferred target for a transport vesicle.

Amino Acid Sequence↗
PubMed1997

Transmembrane domain-dependent sorting of proteins to the ER and plasma membrane in yeast.

Sorting of membrane proteins between compartments of the secretory pathway is mediated in part by their transmembrane domains (TMDs). In animal cells, TMD length is a major factor in Golgi retention. In yeast, the role of TMD signals is less clear; it has been proposed that membrane proteins travel by default to the vacuole, and are prevented from doing so by cytoplasmic signals. We have investigated the targeting of the yeast endoplasmic reticulum (ER) t-SNARE Ufe1p. We show that the amino acid sequence of the Ufe1p TMD is important for both function and ER targeting, and that the requirements for each are distinct. Targeting is independent of Rer1p, the only candidate sorting receptor for TMD sequences currently known. Lengthening the Ufe1p TMD allows transport along the secretory pathway to the vacuole or plasma membrane. The choice between these destinations is determined by the length and composition of the TMD, but not by its precise sequence. A longer TMD is required to reach the plasma membrane in yeast than in animal cells, and shorter TMDs direct proteins to the vacuole. TMD-based sorting is therefore a general feature of the yeast secretory pathway, but occurs by different mechanisms at different points.

Amino Acid Sequence↗
PubMed1997

How order affects the sign test.

In carrying out the sign test, the order in which the subject receives the treatments may be important. We examine Gart's test and show it is equivalent to a score test under a product binomial model. If equal numbers of subjects receive each treatment order, then we suggest our form of Gart's test rather than the sign test should be used routinely.

Binomial Distribution↗
PubMed1994

Inhibition, tissue distribution and hormonal specificity of a promoter-binding factor for the uteroglobin gene.

We had earlier reported a uteroglobin promoter-binding factor in nuclei from progesterone-stimulated rabbit endometrium that was inhibited by a factor in nuclei without progesterone stimulation or from non-target tissues (Rider, V., and Bullock, D.W., 1988. Biochem. Biophys. Res. Comm. 156, 1368-1375). In the course of purification of the inhibitory activity, the effect was shown to be due to contaminating genomic DNA. The inhibitor was destroyed by treatment with DNase I and resisted phenol-chloroform extraction. Fractionation of nuclear extracts on columns of DEAE-Sepharose separated the inhibitor and revealed the presence of binding activity in unstimulated or estrogen-treated endometrium, as well as in liver, lung and ovary. The tissue and hormonal specificity of the promoter binding factor is thus less restricted than recently reported.

Animals↗
PubMed1994

Genomic structure, promoter sequence, and revised translation of human homeobox gene HLX1.

The human homeobox gene HLX1 appears to be involved in hemopoietic development and may represent a candidate gene for various developmental or hemopoietic disorders. We have isolated genomic clones for the gene, determined its intron-exon organization, and confirmed its map location on chromosome 1q41-q42. The transcription initiation sites of HLX1 were identified, and DNA sequences upstream of these sites were established. Finally, several differences between the genomic sequence and the published cDNA sequence were noted. Translation based on this revised sequence gives rise to a putative protein with 86.5% homology to the product of the murine Hlx gene.

Amino Acid Sequence↗
PubMed1994

Control of translation by mRNA secondary structure: the importance of the kinetics of structure formation.

RNA secondary structure is important in a wide variety of biological processes, but relatively little is known about the pathways and kinetics of RNA folding. When the IS10 transposase (tnp) gene is transcribed from a promoter outside the element, little increase in tnp expression is observed. This protection from outside transcription (pot) occurs at the translational level, presumably resulting from mRNA secondary structure proposed to sequester the tnp ribosome-binding site. Here, we confirm the pot RNA structure and show that it blocks 30S ribosomal subunit binding in vitro. Point mutations that abolish protection in vivo map to the pot structure. Surprisingly, these pot mutations do not severely alter the pot secondary structure or increase 30S subunit binding in vitro, except in one case. Using an oligonucleotide hybridization assay, we show that most of the pot mutations slow the kinetics of pot structure formation, with little or no effect on the inhibitory function of the final structure. Moreover, a suppressor mutation reverses this effect. We propose a pathway for pot mRNA folding that is consistent with the mutations and implicates the formation of important kinetic intermediates. The significance of these observations for the RNA folding problem in general is discussed.

Base Sequence↗
PubMed1991

Disease clustering in time.

Tango (1984, Biometrics 40, 15-26) proposed a clustering index for testing for clusters of disease in time. A test based on this clustering index was shown to compare favourably with other statistical tests. In this article we show that Pearson's X2 and its components perform well in testing for clusters of disease in time. The rth of these components identifies a departure from uniformity in moments up to the rth and so helps describe the alternative, if any, to uniformity.

Biometry↗