Search PubMed⌕ Search

Biomedical subjects

L Rask

Publications and source records attributed to L Rask.

At least 127 records · Page 7Linked to original sources
PubMed1985

The primary structure of rabbit and rat prealbumin and a comparison with the tertiary structure of human prealbumin.

The primary structures of rabbit and rat prealbumin have been determined. The amino acid sequence of rabbit prealbumin was determined by analyses of peptides obtained by trypsin and Staphylococcus aureus protease digestions. The rat prealbumin sequence was deduced by analyses of tryptic peptides as well as by nucleotide sequencing of cDNA clones. Both amino acid sequences contain 127 amino acid residues, the same as human prealbumin. Pairwise comparisons show that the three sequences are more than 80% identical. All three prealbumins were found to display significant sequence homology with human thyroxine-binding globulin. A comparison of the primary structures of the prealbumins with the tertiary structure of human prealbumin shows that amino acid replacements are preferentially located at the surface of the molecule and in the loops connecting the beta-strands. The locations of the replacements are discussed as regards the different molecular interactions in which prealbumin is involved.

Amino Acid Sequence↗
PubMed1985

The primary structure of rat liver cellular retinol-binding protein.

The complete amino acid sequence of a cellular retinol-binding protein (CRBP) has been determined for the first time. The primary structure of rat liver CRBP was elucidated by analyses of cyanogen bromide fragments and peptides obtained by tryptic and thermolytic digestions. The single polypeptide chain of rat CRBP consists of 134 amino acid residues. Under reducing conditions, CRBP exists as a monomer, but, in the absence of reducing agents, dimers and multimers of the protein emerge. This is explained by the observation that CRBP contains 3 cysteines, one of which seems to be highly reactive. Whether CRBP contains a disulfide bond is not yet established. The present data extend the previously described homology between CRBP and a family of low molecular weight proteins, all members of which may bind hydrophobic ligands. Since some of these proteins apparently display intracellular transport functions, a similar role for CRBP is envisaged.

Amino Acid Sequence↗
PubMed1985

Gene duplications in the TL region of the mouse major histocompatibility complex.

We have isolated a class I gene from the TL region of the A/J mouse. The gene, T2A, is a homologue of the C57BL/10 mouse gene T2. In the process of mapping this gene we screened a number of BALB/c class I cosmid clusters with a T2A flanking probe. Several of the hybridizing clusters were found to contain identical DNA segments and could therefore be linked together into one single BALB/c TL region which appears to be identical to the TL region of the C57BL/10 mouse. However, two of the hybridizing clusters do not overlap with the C57BL/10 TL region. It appears that these two clusters represent a partial duplication of the TL region in the BALB/c mouse.

Animals↗
PubMed1985

Intron sequences reveal evolutionary relationships among major histocompatibility complex class I genes.

The multigene family of the class I histocompatibility antigens is unusual in that allelic and intergenic differences often are of equal magnitude. It has been suggested that this is due to gene conversion events, which would produce allelic variation but at the same time reduce intergenic differences. We compared the sequences of 11 class I genes in an attempt to elucidate the evolutionary history of this gene family. Our analysis shows that the intron sequences can be used to establish the order of divergence of various class I genes from each other. The results obtained agree with the order of divergence deduced from major insertion and deletion events. It appears that certain genes in the murine TL antigen-encoding region diverged very early from the H-2 and Qa-2,3 genes. The latter can be subgrouped as H-2 and Qa-2,3 genes by both sequence homology and insertion patterns. In contrast to the introns, exon sequences provide less information on evolutionary relationships. Thus, these analyses are consistent with the view that concerted evolution due to gene conversion occurs preferentially in exons.

Animals↗
PubMed1985

Characterization of an HLA DR beta pseudogene.

The class II molecules of the human major histocompatibility complex include the DR, DC, and SB antigens, each composed of an alpha and a beta polypeptide chain. We have isolated a DR beta gene in overlapping cosmid clones made from genomic DNA of a Dw4/DR4 homozygous individual. This gene consists of six exons and spans greater than 20 kilobases. Upon sequencing, it was found to possess several deleterious mutations, each capable of rendering the gene nonfunctional: (i) four splice junctions deviate from the G-T/A-G rule; (ii) two premature termination codons are present in the first domain exon; (iii) a 2-base-pair insertion causes a translational frame shift in the second domain exon. In addition, several amino acid residues that are conserved in all known expressed beta chains have been replaced in the amino acid sequence predicted from the pseudogene. Analysis of the pattern of nucleotide substitutions in the second domain exon suggests that most amino acid replacements occurred after the gene was inactivated. The inactivation may have been caused by insertion of a Kpn I repeat 5' to the promoter region, thereby interfering with transcription of the gene through removal of transcriptional enhancer elements. The DR beta pseudogene seems to be present also in other DR4 individuals.

Amino Acid Sequence↗
PubMed1985

HLA-DR beta genes vary in number between different DR specificities, whereas the number of DQ beta genes is constant.

Probes isolated from DR and DQ beta cDNA and genomic clones were used in hybridizations to restriction enzyme-digested DNA from human homozygous typing cells (HTC) as well as other DR homozygous cells in order to estimate the number of beta genes in the DR/DQ class II region. Varying numbers of DR beta genes were found in HTC of different DR specificities, from possibly one in DR 8 cells to three in cells of DR 2 to 7. The DR beta genes of different specificities seem to be related to one another in a distinct fashion. In contrast, all HTC contain two DQ beta genes per chromosome. The restriction site polymorphism of DQ beta genes is considerably more extensive than that of DQ serology, although one of the genes seems to be nonpolymorphic. In addition to the two DP beta genes identified previously, a minimum of three to five DQ and DR beta genes exist in the human haploid genome.

DNA Restriction Enzymes↗
PubMed1984

Molecular map of the human HLA-SB (HLA-DP) region and sequence of an SB alpha (DP alpha) pseudogene.

The human major histocompatibility complex contains the genes for at least three different types of class II antigens, DR, DC and SB (DR, DQ and DP). They are all composed of an alpha and a beta chain. We have cloned a chromosomal region of 70 kb containing the SB (DP) gene family in overlapping cosmid clones. This segment contains two alpha genes and two beta genes, located in the order SB alpha 1, SB beta 1, SB alpha 2 and SB beta 2. The orientation of the alpha genes is reversed compared with that of the beta genes. This organisation suggests that the SB region has arisen by duplication of a chromosomal segment encompassing one alpha and one beta gene. Partial nucleotide sequences of the SB alpha 1 and SB beta 1 exons demonstrate that the genes correspond to SB alpha and beta cDNA clones. Consequently these genes are expressed. In contrast nucleotide sequence determination of the SB alpha 2 gene shows that it is a pseudogene.

Amino Acid Sequence↗
PubMed1984

Cellular retinol-binding protein. Quantitation and distribution.

The distribution of cellular retinol-binding protein was localized in three tissues involved in the transport of vitamin A using the peroxidase-antiperoxidase technique. In addition, a sensitive radioimmunoassay was developed to quantitate cellular retinol-binding protein in various tissues. In liver, the protein was found in the hepatocytes and in the perisinusoidal fat-storing cells. The columnar epithelial cells of the jejunum and the cells of the proximal tubuli also exhibit high concentrations of cellular retinol-binding protein. Estimations of the content of the protein in various tissues from normal and retinol-deficient rats showed that the retinol status did not affect the tissue levels or the subcellular distribution. The appearance of high amounts of this protein in cells involved in the dietary uptake, storage, mobilization, and resorption of vitamin A suggest that one function of the cellular retinol-binding protein is to act as a vehicle in the intracellular transport of retinol through these organs.

Amino Acid Sequence↗
PubMed1984

Sequence of an epidermal growth factor-binding protein.

A cDNA clone has been isolated that corresponds to the entire translated region of the mRNA coding for the epidermal growth factor-binding protein type B. The complete nucleotide sequence and the predicted amino acid sequence of the protein were elucidated. The protein sequence was compared to some related serine proteases. This comparison supports the notion that several serine proteases suggested to be involved in the processing of precursors to polypeptide hormones and growth factors are closely related to each other. It appears that these proteases are descendants of a common ancestral gene and thus form a distinct subfamily among the serine proteases.

Amino Acid Sequence↗
PubMed1984

Crystallization of and preliminary X-ray data for the plasma retinol-binding protein.

Crystals of the human and rabbit plasma retinol-binding proteins have been grown from solutions of polyethylene glycol 6000 and CdCl2. Two crystal forms have been observed for the human protein, while the rabbit protein has only crystallized in one form which is isomorphous with one of the human serum retinol-binding protein crystals. The crystals differ in their morphologies, but are both in space group P212121 and have similar unit cell sizes (a = 45.9, b = 53.3, c = 72.0 A and a = 45.7, b = 48.7, and c = 76.5 A). The crystals diffract to approximately 2.0 A resolution. In both cases there is 1 molecule/asymmetric unit.

Crystallization↗
PubMed1984

Amino-terminal amino acid sequence of the nonspecific phospholipid exchange protein from bovine liver.

The amino-terminal amino acid sequence of the nonspecific phospholipid exchange protein from bovine liver has been determined. The first 52 amino-terminal residues in the sequence were identified. The sequence determined failed to show statistically significant homology to any previously published protein sequence. However, a stretch of 12 amino acids at the end of the sequence displays homology to the phosphatidylcholine-specific phospholipid exchange protein.

Amino Acid Sequence↗
PubMed1984

7S Nerve growth factor alpha and gamma subunits are closely related proteins.

The polypeptide composition and partial amino acid sequence of the 7S nerve growth factor (NGF) alpha subunit have been determined. Residues in 76 unique positions corresponding to 35% of the molecule were identified. The sequence shows that the NGF alpha subunit is closely related to the NGF gamma subunit and thus a member of the same protein family as the serine proteases. This finding is unexpected since the NGF alpha subunit is devoid of detectable protease activity. However, the NGF alpha subunit differs in one important respect from the NGF gamma subunit and related serine proteases. The highly conserved amino-terminal activation cleavage structure, common to most serine proteases, has been deleted, and an uncleaved activation peptide remains attached to the amino terminus of the mature NGF alpha subunit. It is suggested that this feature is causally related to the apparent lack of proteolytic activity.

Amino Acid Sequence↗
PubMed1984

Both alpha and beta chains of HLA-DC class II histocompatibility antigens display extensive polymorphism in their amino-terminal domains.

At least three class II antigens, all composed of an alpha and a beta subunit, are encoded in the human major histocompatibility complex, i.e., DR, DC and SB. Two cDNA clones, encoding a DC alpha and a DC beta chain, respectively, were isolated from a cDNA library of the lymphoblastoid cell line Raji (DR3,w6). The two polypeptides predicted from the nucleotide sequences of these clones are each composed of a signal peptide, two extracellular domains, a hydrophobic transmembrane region and a short cytoplasmic tail. Comparison of the DC alpha sequence with two previously published partial sequences shows that the majority of the differences is located in the amino-terminal domain. The differences are not randomly distributed; a cluster of replacements is present in the central portion of the amino-terminal domain. Likewise, the allelic polymorphism of the DC beta chains occurs preferentially in the amino-terminal domain, where three minor clusters of replacements can be discerned. The non-random distribution of the variability of DC alpha and beta chains may be due to phenotypic selection against replacement substitutions in the second domains of the polypeptides.

Amino Acid Sequence↗
PubMed1984

The three-dimensional structure of retinol-binding protein.

The complex of retinol with its carrier protein, retinol-binding protein (RBP) has been crystallized and its three-dimensional structure determined using X-ray crystallography. Its most striking feature is an eight-stranded up-and-down beta barrel core that completely encapsulates the retinol molecule. The retinol molecule lies along the axis of the barrel with the beta-ionone ring innermost and the tip of the isoprene tail close to the surface.

Animals↗
PubMed1984

Mutations and selection in the generation of class II histocompatibility antigen polymorphism.

A comparison of seven human DR and DC class II histocompatibility antigen beta-chain amino acid sequences indicates that the allelic variation is of comparable magnitude within the DR and DC beta-chain genes. Silent and replacement nucleotide substitutions in six DR and DC beta-chain sequences, as well as in seven murine class II sequences (three I-A beta and four I-A alpha alleles) were analyzed. The results suggest that the mutation rates are of a comparable magnitude in the nucleotide sequences encoding the first and second external domains of the class II molecules. Nevertheless, the allelic amino acid replacements are predominantly located in the first domains. We conclude that a conservative selective pressure acts on the second domains, whereas in many positions in the first domains replacement substitutions are selectively neutral or maybe even favoured. Thus, the difference between the first and second domains as regards the number of amino acid replacements is mainly due to selection.

Amino Acid Sequence↗
PubMed1984

The Eb beta gene may have acted as the donor gene in a gene conversion-like event generating the Abm 12 beta mutant.

At least two different class II histocompatibility antigens, I-A and I-E, are encoded by the murine major histocompatibility complex. Both types of class II antigens are composed of polypeptide chains called alpha and beta. Class II antigens display extensive genetic polymorphism, the main part of which resides in the NH2-terminal domains of the A alpha, A beta and E beta chains. Recently it was shown that the mutant gene Abm 12 beta differed from the wild-type gene Ab beta by three nucleotide substitutions, which all occur within a stretch of 14 nucleotides. Multiple substitutions of the type found in the Abm 12 beta gene suggest that the mutant arose by a gene conversion-like event. To examine whether the Eb beta gene may have served as the donor gene in the generation of the Abm 12 beta gene, we have isolated and sequenced a cDNA clone corresponding to the Eb beta gene. Comparisons of the Eb beta, the Ab beta and the Abm 12 beta nucleotide sequences revealed that the Eb beta sequence is identical to that of Abm 12 beta in the positions where the latter differs from the Ab beta sequence. This observation is consistent with the notion that the Abm 12 beta mutant gene arose by a gene conversion-like event involving the Eb beta gene.

Alleles↗