Mapping of the residues responsible for the negative cooperativity of the receptor-binding region of insulin.

Abstract:

:Insulin binding to its receptor leads to negatively cooperative interactions among the receptor sites. Studies with 29 insulin analogues (animal insulins and proinsulin, insulin-like growth factor and chemically modified insulins) which vary 1,000-fold in their affinity for the receptor and in their biological potency, suggest that a discrete invariable region on the surface of the insulin monomer is responsible for including the negative cooperativity. This domain comprises some of the eight carboxy-terminal residues of the B-chain and the A21 asparagine. Burying of this 'cooperative site' in the dimerisation of insulin leads to a loss of negative cooperativity. A revised mapping of the insulin molecule is proposed, featuring distinct bioactive and cooperative sites.

journal_name

Nature

journal_title

Nature

authors

De Meyts P,Van Obberghen E,Roth J

doi

10.1038/273504a0

subject

Has Abstract

pub_date

1978-06-15 00:00:00

pages

504-9

issue

5663

eissn

0028-0836

issn

1476-4687

journal_volume

273

pub_type

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