PubMed Health⌕ Search

Biomedical subjects

C J Soames

Publications and source records attributed to C J Soames.

5 recordsLinked to original sources
PubMed1997

Interactions between human complement components factor H, factor I and C3b.

Using a microtitre plate assay, direct binding between complement factors I and H was demonstrated, and ligand blotting indicated that factor H interacts with the heavy chain of factor I. Similarly, direct C3(NH3)-factor I and C3(NH3)-factor H binding was characterized [where C3(NH3) is a form of C3 that is cleaved by factor I in the presence of factor H]. Both factor H and factor I interacted with both chains of C3(NH3) in ligand blotting. Binding reactions between all three pairs of components were highly dependent on ionic strength, and showed similar pH optima. Binding assays with all three components present led to the following conclusions. (a) Binding sites for C3(NH3) and factor I on factor H do not overlap, and binding of factor I and C3(NH3) to soluble factor H promotes the weak factor I-C3(NH3) interaction. (b) Anomalies arise with immobilized factor H, which may be artefactual or may reflect the physiological situation. (c) Similarly, binding sites on factor I for C3(NH3) and for factor H do not overlap, and binding of factor H and C3(NH3) to factor I promotes direct factor H-C3(NH3) interactions. Based on these results, a model of the interactions between factor H, factor I and C3(NH3) leading to the processing of C3(NH3) is proposed.

Cations, Divalent↗
PubMed1996

Identification of regions of the Wiskott-Aldrich syndrome protein responsible for association with selected Src homology 3 domains.

Src homology 3 (SH3) domains have been shown to mediate selected interactions between signaling molecules and are essential for the activation of a number of receptor-driven pathways. The Wiskott-Aldrich syndrome protein was identified as a protein that associated selectively with the SH3 domains derived from c-Src, p85alpha, phospholipase Cgamma1, and c-Fgr. Significantly reduced association was detected to the N-terminal SH3 domain and the tandem SH3 domains of p47(phox), and no binding was detected to the SH3 domain of n-Src, the C-terminal SH3 domain of p47(phox), or either of the SH3 domains of p67(phox). Three peptides corresponding to potential Wiskott-Aldrich syndrome protein SH3 domain binding motifs were found to inhibit its association with c-Src, Fgr, and phospholipase Cgamma1 SH3 domains, but not the p85alpha SH3 domain. These peptides have the sequences MRRQEPLPPPPPPSRG, TGRSGPLPPPPPGA, and KGRSGPLPPVPLGI and show homology with other SH3 domain binding motifs. It is possible that the intracellular association of Wiskott-Aldrich syndrome protein with other signaling proteins is mediated by its SH3 domain-binding regions, and this may play a role in its putative function as a regulatory molecule in immune cells.

Amino Acid Sequence↗
PubMed1996

Prediction from sequence comparisons of residues of factor H involved in the interaction with complement component C3b.

The amino acid sequence of the region of bovine factor H containing the C3b binding site has been derived from sequencing overlapping cDNA clones. A cDNA sequence encoding 669 amino acids was obtained. Like human and mouse factor H the sequence can be arranged into a number of internally homologous units (CPs), each of which is about 60 amino acids long and is based on a framework of four conserved cysteine residues. Bovine factor H is of the same molecular mass as human and mouse factor H, and is therefore likely to be composed of 20 contiguous CPs. Comparisons with human and mouse factor H indicate that the partial bovine sequence encodes CPs 2-12 inclusive of bovine factor H. Bovine factor H binds to human ammonia-treated C3 (causing thiolester cleavage) [C3(NH3)] and promotes the cleavage of human C3(NH3) in the presence of bovine factor I. Other studies indicate that CPs 2-5 of human factor H encompass the C3b binding and factor I cofactor activity site. Multiple sequence alignments of human factor H, mouse factor H (which also interacts with human C3b) and bovine factor H with CP modules whose structures have been determined experimentally, have been used to predict residues in the hypervariable loops of CPs 2-5 and to identify residues of potential importance in human C3 binding and factor I cofactor activity. Leu-17 and Gly-20 of CP 2, Ser-17, Ala-19, Glu-21, Asp-23 and Glu-25 of CP 3 and Lys-18 of CP 4 are all conserved between the three species. It may be that CPs 3 and 4 interact with C3(NH3) directly, whilst CPs 2 and 5 maintain the correct orientation for CPs 3 and 4 to interact.

Amino Acid Sequence↗