Importance of the character and configuration of residues B24, B25, and B26 in insulin-receptor interactions

Journal Article · Fri Jan 25 04:00:00 EST 1991 · Journal of Biological Chemistry; (USA)

OSTI ID:6057913

Mirmira, R G; Nakagawa, S H; Tager, H S ^[1]

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1. Univ. of Chicago, IL (USA)

By use of isolated canine hepatocytes and insulin analogs prepared by trypsin-catalyzed semisynthesis, we have investigated the importance of the aromatic triplet PheB24-PheB25-TyrB26 of the COOH-terminal B-chain domain of insulin in directing the affinity of insulin-receptor interactions. Analysis of the receptor binding potencies of analogs bearing transpositions or replacements (by Tyr, D-Tyr or their corresponding 3,5-diiodo derivatives) in this region demonstrates a wide divergence in the acceptance both of configurational change (with (D-TyrB24,PheB26)insulin and (D-TyrB25,PheB26)insulin exhibiting 160 and 0.1% of the receptor binding potency of insulin, respectively) and of detailed side chain structure (with (TyrB24,PheB26)insulin and (TyrB25,PheB26)insulin exhibiting 2 and 80% of the receptor binding potency of insulin, respectively). Additional experiments addressed the solvent accessibilities of the 4 tyrosine residues of insulin and the insulin analogs at selected peptide concentrations by use of analytical radioiodination. Whereas two analogs ((TyrB25,PheB26)insulin and (D-TyrB24,PheB26)insulin) were found to undergo self aggregation, no strict correlation was found between the ability of an analog to aggregate and its potency for interaction with the insulin receptor. Related findings are discussed in terms of the interplay between side chain and main chain structure in the COOH-terminal domain of the insulin B-chain and the structural attributes of insulin that determine the affinity of insulin-receptor interactions.

• OSTI ID: 6057913
• Journal Information: Journal of Biological Chemistry; (USA), Journal Name: Journal of Biological Chemistry; (USA) Vol. 266:3; ISSN JBCHA; ISSN 0021-9258
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AFFINITY
AMINO ACID SEQUENCE
AMINO ACIDS
ANIMAL CELLS
ANIMALS
BIOCHEMICAL REACTION KINETICS
CARBOXYLIC ACIDS
CHEMICAL COMPOSITION
DOGS
HORMONES
HYDROXY ACIDS
INSULIN
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LIVER CELLS
MAMMALS
MEMBRANE PROTEINS
MOLECULAR STRUCTURE
ORGANIC ACIDS
ORGANIC COMPOUNDS
PEPTIDE HORMONES
PROTEINS
REACTION KINETICS
RECEPTORS
RESIDUES
SOMATIC CELLS
STRUCTURE-ACTIVITY RELATIONSHIPS
TRACER TECHNIQUES
TYROSINE
VERTEBRATES