Biomedical subjects

J Coadwell

Publications and source records attributed to J Coadwell.

24 records · Page 2Linked to original sources

PubMed1990

Nucleotide sequences and three-dimensional modelling of the VH and VL domains of two human monoclonal antibodies specific for the D antigen of the human Rh-blood-group system.

The nucleotide sequences were determined for the VH and VL domains of two human IgG1 antibodies, Pag-1 and Fog-B, specific for the D antigen of the Rh-blood-group system. The VH-region genes of the two antibodies were derived from separate germ-line genes within the VH-IV gene family, but both antibodies used the same JH6 gene. The D-region genes differed from each other, and no similarity was found to known D regions. The light chain of Fog-B belongs to the V lambda-I subgroup and that of Pag-1 probably belongs to the V lambda-V subgroup; both light chains used the J2/3 gene. Three-dimensional models of the variable domains were made, based on those of known crystallographic structure. The surface contours at the combining sites are clearly different, consistent with the evidence that the antibodies recognize different but overlapping epitopes. Some details of the molecular modelling of hypervariable regions have been deposited as Supplementary Publication SUP 50155 (6 pages) at the British Library Document Supply Centre, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1990) 265, 5.

Amino Acid Sequence↗

PubMed1989

Some observations on conserved polar side chains in immunoglobulin V-domains.

1. The roles of conserved polar residues have been studied in 12 V-domains for which atomic coordinates are available. 2. In most cases a particular residue had a similar side chain conformation in all V-domains examined and the polar group provided the same hydrogen bonds which helped to stabilize the conformations of the domains. 3. In the case of a conserved glutamine/glutamic acid residue the buried side chain could adopt a variety of conformations and the polar group could form different hydrogen bonds from one domain to another. However, they contributed similarly to domain stability. 4. In the case of a conserved threonine/serine residue its side chain showed relative rotations of up to 180 degrees from one domain to another. The hydroxyl group could be buried or exposed at the domain surface. In some domains it formed hydrogen bonds to two other protein atoms but in other domains there was a single hydrogen bond or none at all. The varied roles of this residue are discussed in the text.

Aspartic Acid↗

PubMed1989

Some observations on the replacement of the conserved amino acid residues of immunoglobulin domains.

1. Computer graphics have been used to model replacements of conserved residues in immunoglobulin domains. 2. Replacements, even those involving large changes in side chain volume, could be accommodated in the domain but rotation and repacking of surrounding side chains was generally necessary. 3. Repacking often resulted in increases in inter-atomic distances between side chains and loss of some van der Waals' contacts. This would be expected to make the domain slightly less stable. 4. Losses in domain stability might not have a serious affect on antigen binding but could result in circulating antibody becoming more susceptible to biological degradation with considerable reduction in biological half-life.

Alanine↗

PubMed1987

The sites of tryptic cleavage in bovine secretory component: structural and functional implications.

Tryptic fragments from bovine secretory component and sIgA have been separated by HPLC and/or SDS polyacrylamide gel electrophoresis and electroblotting. Their N-terminal amino acid sequences have been determined and their positions in the secretory component molecule deduced by homology with the amino acid sequences of human secretory component and rabbit polyimmunoglobulin receptor. Taken in conjunction with the known binding affinities of the tryptic fragments, the results imply that the three most N-terminal domains of secretory component are directly involved in binding IgM and IgA dimers. The results also favour the concept of an extended 'zig-zag' structure for the secretory component molecule.

Amino Acid Sequence↗

PubMed1987

Tertiary structures for the extracellular domains of the epithelial polyimmunoglobulin receptor (secretory component) derived by primary structure comparisons with immunoglobulins.

The amino acid sequences of the rabbit receptor and human secretory component (SC) domains have been compared with those of immunoglobin (Ig) domains. Accessible and inaccessible sites of tryptic cleavage in bovine SC have been located by sequence homology. Computerized secondary structure prediction and three dimensional model building have been carried out. The resulting tertiary structures are extremely Ig-like consisting of two superposed beta-pleated sheets. All carbohydrate sites lie at external positions as do tryptic cleavage sites. Potential sites for tryptic hydrolysis that are not cleaved lie at buried or partially buried positions. 6. Inter-beta-sheet contact between domains appears to be highly unlikely so that the quaternary structure is largely determined by longitudinal contacts.

Amino Acid Sequence↗

PubMed1986

Unusual features of the T-cell receptor C domains are revealed by structural comparisons with other members of the immunoglobulin superfamily.

The amino acid sequences of the domains of human, mouse and rabbit T-cell antigen receptors have been aligned with those of immunoglobulin domains of known three-dimensional structure. Computerized secondary structure predictions have been performed on the sequences and putative models of the domains have been constructed. The receptor V alpha and V beta domains are closely related to immunoglobulin VH domains. The receptor C alpha domain shows some major divergences from immunoglobulin C domains and the C beta domain displays an unusual feature. The implications for T-cell receptor function are discussed.

Amino Acid Sequence↗