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Identification of amyloid prealbumin variant in familial amyloidotic polyneuropathy (Japanese type)
Abstract:
Structural studies on an amyloid fibril protein of 14 K daltons (AFj(INO] isolated from a Japanese patient who suffered from familial amyloidotic polyneuropathy were carried out to unambiguously identify its difference from normal human serum prealbumin. Sequence analyses performed by comparing peptide maps prepared from cyanogen bromide fragments and tryptic peptides of purified RCM-amyloid protein with those from RCM-prealbumin indicate that only a valine residue at position 30 in prealbumin is replaced by a methionine residue. Furthermore, it was also proved that AFj(INO) consists of four components; the prealbumin variant and its three related proteins, which are derived by successively accumulated deletion of the N-terminal three amino acid residues (Gly1, Pro2 and Thr3) from the prealbumin variant.
Insights
Researchers identified a unique amyloid fibril protein variant in familial amyloidotic polyneuropathy. This variant differs from normal prealbumin by a single amino acid substitution and N-terminal deletions.
Area of Science:
- Biochemistry
- Molecular Biology
- Protein Chemistry
Background:
- Familial amyloidotic polyneuropathy (FAP) is a hereditary disease characterized by amyloid deposition.
- Amyloid fibril proteins are often variants of normal serum proteins.
- Prealbumin (transthyretin) is a known precursor protein for some forms of FAP.
Purpose of the Study:
- To structurally characterize the amyloid fibril protein (AFj(INO)) isolated from a Japanese FAP patient.
- To determine the differences between AFj(INO) and normal human serum prealbumin.
- To elucidate the composition of the isolated amyloid fibril protein.
Main Methods:
- Protein purification of amyloid fibril protein (AFj(INO)) and normal prealbumin.
- Cyanogen bromide fragmentation and tryptic peptide mapping for sequence analysis.
- Comparison of peptide maps to identify amino acid substitutions and deletions.
Main Results:
- The amyloid fibril protein AFj(INO) differs from normal prealbumin by a single amino acid substitution: valine at position 30 is replaced by methionine.
- AFj(INO) is composed of four protein components.
- These components include the prealbumin variant and three related proteins with successive N-terminal deletions of Glycine, Proline, and Threonine residues.
Conclusions:
- The identified prealbumin variant is the primary component of the amyloid fibrils in this Japanese FAP patient.
- The successive N-terminal deletions suggest a post-translational modification or degradation process.
- Understanding these structural variations is crucial for FAP pathogenesis research.