High affinity insulin binding by soluble insulin receptor extracellular domain fused to a leucine zipper.

Abstract:

:Insulin receptors (IRs) that are truncated at the end of the ectodomain form dimers that bind insulin with different characteristics to wild type receptors. These soluble IRs have lowered affinity for insulin compared with full-length IR, and exhibit linear Scatchard plots in contrast to the curvilinear plots obtained with full-length IR, IR truncated at the C-terminus of the transmembrane region and IR ectodomains fused to the self-associating constant domains from Fc or lambda immunoglobulins. In this report, we have fused the IR ectodomain to the 33 residue leucine zipper from the transcriptional activator GCN4 of Saccharomyces cerevisiae. This fusion protein binds insulin with high affinity in a manner comparable to native receptor. The respective dissociation constants were Kd1 8.2 X 10(-11) M and Kd2 1.6 x 10(-8) M for hIRedZip and Kd1 5.7 x 10(-11) M and Kd2 6.3 x 10(-9) M for membrane-anchored, native receptor.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Hoyne PA,Cosgrove LJ,McKern NM,Bentley JD,Ivancic N,Elleman TC,Ward CW

doi

10.1016/s0014-5793(00)01872-x

keywords:

subject

Has Abstract

pub_date

2000-08-11 00:00:00

pages

15-8

issue

1-2

eissn

0014-5793

issn

1873-3468

pii

S0014-5793(00)01872-X

journal_volume

479

pub_type

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