Primary structure of an amyloid prealbumin variant in familial polyneuropathy of Jewish origin
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Abstract:
The complete amino acid sequence of three related amyloid proteins (Mr 14,000, 10,000, and 5,000) derived from tissues of a Jewish patient who suffered from a variant of familial polyneuropathic amyloidosis was determined. The protein, which contains 127 residues, is identical to a human serum prealbumin subunit. Only one amino acid substitution, glycine for threonine, was detected at position 49, where enzymatic cleavage occurred, yielding Mr 5,000 and 10,000 fragments which represent the amino terminus (residues 1-48) and carboxyl terminus (residues 49-127) of the molecule, respectively. Thus, a prealbumin variant and its fragments constitute the amyloid fibrils in a heredofamilial amyloidosis syndrome of dominant inheritance.
Insights
Researchers identified a prealbumin variant and its fragments as amyloid fibrils in familial polyneuropathic amyloidosis. This genetic condition, linked to a specific amino acid substitution, causes dominant inheritance of the disease.
Area of Science:
- Biochemistry
- Genetics
- Neurology
Background:
- Familial amyloidosis syndromes are inherited disorders characterized by the deposition of amyloid fibrils in various tissues.
- Amyloid deposition can lead to progressive organ dysfunction and severe clinical manifestations, such as polyneuropathy.
Purpose of the Study:
- To determine the complete amino acid sequence of amyloid proteins found in a patient with a variant of familial polyneuropathic amyloidosis.
- To elucidate the molecular basis of amyloid fibril formation in this specific heredofamilial amyloidosis syndrome.
Main Methods:
- Amino acid sequencing of amyloid proteins isolated from patient tissues.
- Analysis of protein structure and identification of amino acid substitutions.
- Enzymatic cleavage to characterize protein fragments.
Main Results:
- Three related amyloid proteins (Mr 14,000, 10,000, and 5,000) were identified.
- The primary protein (127 residues) is identical to a human serum prealbumin subunit with a glycine for threonine substitution at position 49.
- Enzymatic cleavage at position 49 yielded fragments corresponding to the amino and carboxyl termini.
Conclusions:
- A prealbumin variant, characterized by a specific amino acid substitution, is the constituent of amyloid fibrils in this familial amyloidosis.
- The findings indicate that this prealbumin variant and its fragments are responsible for the amyloidosis observed in this dominant inheritance syndrome.