Title : A nucleotide insertion and frameshift cause
albumin Kénitra , an extended and O-glycosylated mutant of human serum
albumin with two additional disulfide bridges
Abstract :
- Albumin Kenitra is a new type of genetic variant of human serum albumin that has been found in two members of a family of Sephardic Jews from Kenitra (Morocco)
- The slow-migrating variant and the normal protein were isolated by anion-exchange chromatography and, after treatment with CNBr, the digests were analyzed by two-dimensional electrophoresis in a polyacrylamide gel
- The CNBr peptides of the variant were purified by reverse-phase high performance liquid chromatography and submitted to sequence analysis
- Albumin Kenitra is peculiar because it has an elongated polypeptide chain, 601 residues instead of 585, and its sequence is modified beginning from residue 575
- DNA structural studies showed that the variant is caused by a single-base insertion, an adenine at nucleotide position 15 970 in the genomic sequence , which leads to a frameshift with the subsequent translation to the first termination codon of exon 15
- Mass spectrometric analyses revealed that the four additional cysteine residues of the variant form two new S-S bridges and showed that albumin Kenitra is partially O-glycosylated by a monosialylated HexHexNAc structure.
- This oligosaccharide chain has been located to Thr596 by amino-acid sequence analysis of the tryptic fragment 592-597