Amino acid sequence requirements in the human IgAI hinge for cleavage by streptococcal IgAI proteases

2002 ◽  
Vol 30 (4) ◽  
pp. 516-518 ◽  
Author(s):  
B. W. Senior ◽  
M. R. Batten ◽  
M. Kilian ◽  
J. M. Woof
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Sequence ◽  
Peptide Bond ◽  
Major Effect ◽  
Functional Abilities ◽  
Pathogenic Species ◽  
Α Chain ◽  
Sequence Requirements

All the IgA1 proteases of the different pathogenic species of Streptococcus cleave the hinge of the α chain of human IgA1 only at one proline-threonine peptide bond. In order to study the importance of these amino acids for cleavage, several hinge mutant recombinant IgA1 antibodies were constructed. The mutations were found to be without major effect upon the structure or functional abilities of the antibodies. However, they had a major effect upon their sensitivity to cleavage by some of the IgA1 proteases.

scholarly journals Amino Acid Sequence Requirements in the Hinge of Human Immunoglobulin A1 (IgA1) for Cleavage by Streptococcal IgA1 Proteases

2003 ◽  
Vol 71 (3) ◽  
pp. 1462-1469 ◽  
Author(s):  
Margaret R. Batten ◽  
Bernard W. Senior ◽  
Mogens Kilian ◽  
Jenny M. Woof
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Single Point ◽  
Point Mutations ◽  
Peptide Bond ◽  
Human Immunoglobulin ◽  
Single Point Mutation ◽  
Absolute Requirement ◽  
Iga1 Protease ◽  
Sequence Requirements

ABSTRACT The amino acid sequence requirements in the hinge of human immunoglobulin A1 (IgA1) for cleavage by IgA1 proteases of different species of Streptococcus were investigated. Recombinant IgA1 antibodies were generated with point mutations at proline 227 and threonine 228, the residues lying on either side of the peptide bond at which all streptococcal IgA1 proteases cleave wild-type human IgA1. The amino acid substitutions produced no major effect upon the structure of the mutant IgA1 antibodies or their functional ability to bind to Fcα receptors. However, the substitutions had a substantial effect upon sensitivity to cleavage with some streptococcal IgA1 proteases, with, in some cases, a single point mutation rendering the antibody resistant to a particular IgA1 protease. This effect was least marked with the IgA1 protease from Streptococcus pneumoniae, which showed no absolute requirement for either proline or threonine at residues 227 to 228. By contrast, the IgA1 proteases of Streptococcus oralis, Streptococcus sanguis, and Streptococcus mitis had an absolute requirement for proline at 227 but not for threonine at 228, which could be replaced by valine. There was evidence in S. mitis that proteases from different strains may have different amino acid requirements for cleavage. Remarkably, some streptococcal proteases appeared able to cleave the hinge at a distant alternative site if substitution prevented efficient cleavage of the original site. Hence, this study has identified key residues required for the recognition of the IgA1 hinge as a substrate by streptococcal IgA1 proteases, and it marks a preliminary step towards development of specific enzyme inhibitors.

Nucleotide sequence of complementary DNA and derived amino acid sequence of murine complement protein C3

1984 ◽  
Vol 306 (1129) ◽  
pp. 333-344 ◽  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Sequence ◽  
Transition Region ◽  
Sequence Homology ◽  
Complement Protein ◽  
Single Chain ◽  
Complementary Dna ◽  
Α Chain ◽  
Β Chain

The nucleotide sequences coding for murine complement component C3 have been determined from a cloned genomic DNA fragment and several overlapping cloned complementary DNA fragments. The amino acid sequence of the protein was deduced. The mature β and α subunits contain 642 and 993 amino acids respectively. Including a 24 amino acid signal peptide and four arginines in the β—α transition region, which are probably not contained in the mature protein, the unglycosylated single chain precursor protein preproC3 would have a molecular mass of 186484 Da and consist of 1663 amino acid residues. The C3 messenger RNA would be composed of a 56 + 2 nucleotide long 5' non-translated region, 4992 nucleotides of coding sequence, and a 3' non-translated region of 39 nucleotides, excluding the poly A tail. The β chain contains only three cysteine residues, the α chain 24, ten of which are clustered in the carboxy terminal stretch of 175 amino acids. Two potential carbohydrate attachment sites are predicted for the α chain, none for the β chain. From a comparison with human C3 cDNA sequence (of which over 80% has been determined) an extensive overall sequence homology was observed. Human and murine preproC3 would be of very similar length and share several noteworthy properties: the same order of the subunits in the precursor, the same basic residue multiplet in the β-a transition region, and a glutamine residue in the thioester region. The equivalent position of the known factor I cleavage sites in human C3a could be located in the murine C3 α chain and the size and sequence of the resulting peptide were deduced. A comparison of the amino acid sequences of murine G3 and human alpha2-macroglobulin is given. Several areas of strong sequence homology are observed, and we conclude that the two genes must have evolved from a common ancestor.

Complete Covalent Structure of Human Platelet Factor 4

1979 ◽  
Vol 42 (05) ◽  
pp. 1652-1660 ◽  
Author(s):  
Francis J Morgan ◽  
Geoffrey S Begg ◽  
Colin N Chesterman
Keyword(s):  
Amino Acids ◽  
Molecular Weight ◽  
Amino Acid ◽  
Amino Acid Sequence ◽  
Human Platelet ◽  
Platelet Factor 4 ◽  
Platelet Factor ◽  
Disulphide Bonds ◽  
Covalent Structure

SummaryThe amino acid sequence of the subunit of human platelet factor 4 has been determined. Human platelet factor 4 consists of identical subunits containing 70 amino acids, each with a molecular weight of 7,756. The molecule contains no methionine, phenylalanine or tryptophan. The proposed amino acid sequence of PF4 is: Glu-Ala-Glu-Glu-Asp-Gly-Asp-Leu-Gln-Cys-Leu-Cys-Val-Lys-Thr-Thr-Ser- Gln-Val-Arg-Pro-Arg-His-Ile-Thr-Ser-Leu-Glu-Val-Ile-Lys-Ala-Gly-Pro-His-Cys-Pro-Thr-Ala-Gin- Leu-Ile-Ala-Thr-Leu-Lys-Asn-Gly-Arg-Lys-Ile-Cys-Leu-Asp-Leu-Gln-Ala-Pro-Leu-Tyr-Lys-Lys- Ile-Ile-Lys-Lys-Leu-Leu-Glu-Ser. From consideration of the homology with p-thromboglobulin, disulphide bonds between residues 10 and 36 and between residues 12 and 52 can be inferred.

SOME ASPECTS OF THE STRUCTURE OF HEMOGLOBIN

1964 ◽  
Vol 42 (6) ◽  
pp. 755-762 ◽  
Author(s):  
David B. Smith
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Sequence ◽  
Partial Amino Acid Sequence ◽  
Heme Pocket ◽  
Terminal Amino ◽  
Polypeptide Chains ◽  
Kinetics Of ◽  
Β Chain

An outline of present ideas concerning the arrangement, folding, and chemistry of the polypeptide chains of hemoglobin is given with some references to present know ledge of myoglobin.New material includes a partial amino acid sequence of the β-chain of horse hemoglobin, details concerning the amino acids lining the heme pocket of horse hemoglobin, and the effects of carboxypeptidases A and B on horse oxy- and horse deoxy-hemoglobin. The kinetics of the latter reactions are not simple. The C-terminal amino acids are released more rapidly from the oxygenated form.

scholarly journals The amino acid sequence of cytochromes c-551 from three species of Pseudomonas

1973 ◽  
Vol 131 (3) ◽  
pp. 485-498 ◽  
Author(s):  
R. P. Ambler ◽  
Margaret Wynn
Keyword(s):  
Amino Acids ◽  
Pseudomonas Aeruginosa ◽  
Amino Acid ◽  
Cytochrome C ◽  
Amino Acid Sequence ◽  
Amino Acid Sequences ◽  
Mitochondrial Cytochrome ◽  
Cytochromes C ◽  
Lending Library ◽  
Single Peptide

The amino acid sequences of the cytochromes c-551 from three species of Pseudomonas have been determined. Each resembles the protein from Pseudomonas strain P6009 (now known to be Pseudomonas aeruginosa, not Pseudomonas fluorescens) in containing 82 amino acids in a single peptide chain, with a haem group covalently attached to cysteine residues 12 and 15. In all four sequences 43 residues are identical. Although by bacteriological criteria the organisms are closely related, the differences between pairs of sequences range from 22% to 39%. These values should be compared with the differences in the sequence of mitochondrial cytochrome c between mammals and amphibians (about 18%) or between mammals and insects (about 33%). Detailed evidence for the amino acid sequences of the proteins has been deposited as Supplementary Publication SUP 50015 at the National Lending Library for Science and Technology, Boston Spa, Yorks. LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1973), 131, 5.

Correction to the Amino Acid Sequence of the α Chain of Human Haptoglobin

1973 ◽  
Vol 51 (3) ◽  
pp. 321-322 ◽  
Author(s):  
B. Malchy ◽  
G. H. Dixon
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Α Chain

The previously published amino acid sequence of the α chain of human haptoglobin must be corrected to include a half-cystine residue at position 73.

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