Molecular and functional characterization of amylin, a peptide associated with type 2 diabetes mellitus
- Univ. of Oxford (England)
- Univ. of Oxford (England) Medical Research Council Radiobiology Unit, Chilton (England)
The 37-amino acid peptide called amylin is a major component of the islet amyloid deposited in the pancreases of persons with type 2 diabetes mellitus. The authors report the isolation of a partial cDNA clone and a phage {lambda} genomic clone of the coding region of the amylin gene. The DNA sequence encodes a protein sequences identical to that of amylin isolated from the amyloid found in the diabetic pancreas and shows that amylin is likely to be synthesized as a precursor peptide, now named proamylin. They have demonstrated that the amylin gene is present on chromosome 12 and that it is probably transcribed in the islets of Langerhans. The sequences of the genes for amyli and the calcitonin gene-related peptides (CGRPs) show strong similarity, especially over their 5{prime} coding regions, where both peptides have a conserved intramolecular disulfide bridge, and also over their 3{prime} coding regions, where the presence of a glycine codon strongly suggests that the carboxylterminal residue of amylin, like that of CGRP, is amidated. To examine the functional relevance of these posttranslational modifications, the biological activity of amylin synthesized with or without the disulfide bridge and/or amidation was measured. It was found that both features are necessary for full biological activity, thereby confirming the functional importance of those regions of the molecule whose sequences are conserved at both protein and genetic levels.
- OSTI ID:
- 7138301
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America; (USA), Vol. 86:24; ISSN 0027-8424
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
DIABETES MELLITUS
PATHOGENESIS
GLYCOGEN
BIOSYNTHESIS
PEPTIDES
MOLECULAR STRUCTURE
RECOMBINANT DNA
DNA SEQUENCING
PANCREAS
PATIENTS
BODY
CARBOHYDRATES
DIGESTIVE SYSTEM
DISEASES
DNA
ENDOCRINE DISEASES
ENDOCRINE GLANDS
GLANDS
METABOLIC DISEASES
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANS
POLYSACCHARIDES
PROTEINS
SACCHARIDES
STRUCTURAL CHEMICAL ANALYSIS
SYNTHESIS
550200* - Biochemistry