The Ile-84 → Ser amino acid substitution in transthyretin interferes with the interaction with plasma retinol-binding protein

Rodolfo Berni, Giorgio Malpeli, Claudia Folli, Jill R. Murrell, Juris J. Liepnieks, Merrill Benson

Research output: Contribution to journalArticle

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Abstract

In plasma the thyroid hormone-binding protein transthyretin (TTR) forms a tight complex with the specific retinol carrier retinol-binding protein (RBP). The Ile-84 → Ser mutation and several other point mutations in TTR are associated with familial amyloidotic polyneuropathy, which is characterized by extracellular depositions of amyloid fibrils mainly consisting of mutated TTRs. The interactions with human RBP of recombinant human normal and Ser-84 TTRs were investigated by monitoring the fluorescence anisotropy of RBP-bound retinol. A nearly negligible affinity of the recombinant Ser-84 TTR for RBP was found. This result indicates the participation of a region on the outer surface of TTR that comprises Ile-84 in the recognition of RBP. In preliminary studies the Ser-84 TTR was the only one among several amyloidogenic variant TTRs to display negligible interaction with RBP. Therefore, in general a substantially altered binding of TTR to RBP is not associated with familial amyloidotic polyneuropathy. Instead, the altered binding of Ser-84 TTR to RBP appears to be responsible for an abnormal plasma transport of RBP. The recombinant normal TTR exhibits binding properties, in its interaction with human RBP, approximately similar to those of TTR purified from human plasma. Two independent and equivalent RBP binding sites on recombinant normal TTR are characterized by a dissociation constant of about 0.4 μM.

Original languageEnglish
Pages (from-to)23395-23398
Number of pages4
JournalJournal of Biological Chemistry
Volume269
Issue number38
StatePublished - Sep 23 1994

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Plasma Retinol-Binding Proteins
Retinol-Binding Proteins
Prealbumin
Beam plasma interactions
Amino Acid Substitution
Substitution reactions
Amino Acids
Polyneuropathies
Vitamin A
Plasma (human)
Fluorescence Polarization
Plasmas
Point Mutation
Amyloid
Protein Binding

ASJC Scopus subject areas

  • Biochemistry

Cite this

The Ile-84 → Ser amino acid substitution in transthyretin interferes with the interaction with plasma retinol-binding protein. / Berni, Rodolfo; Malpeli, Giorgio; Folli, Claudia; Murrell, Jill R.; Liepnieks, Juris J.; Benson, Merrill.

In: Journal of Biological Chemistry, Vol. 269, No. 38, 23.09.1994, p. 23395-23398.

Research output: Contribution to journalArticle

Berni, Rodolfo ; Malpeli, Giorgio ; Folli, Claudia ; Murrell, Jill R. ; Liepnieks, Juris J. ; Benson, Merrill. / The Ile-84 → Ser amino acid substitution in transthyretin interferes with the interaction with plasma retinol-binding protein. In: Journal of Biological Chemistry. 1994 ; Vol. 269, No. 38. pp. 23395-23398.
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