Recognition of an antiparallel beta-sheet structure of human epidermal growth factor by its receptor. Site-directed mutagenesis studies of Ala-30 and Asn-32.

Abstract:

:The Ala-30 and Asn-32 residues involved in the major antiparallel beta-sheet structure of human epidermal growth factor (hEGF) were substituted with various amino acid residues, and the receptor-binding affinities of the nine variant hEGFs were determined by the use of human KB cells. The Ala-30----Arg, Ala-30----His and Ala-30----Phe substitutions drastically reduced the binding affinity, suggesting that the side chain in position 30 of Ala-30 of hEGF is required to be small for the receptor binding. The Asn-32----Asp substitution significantly reduced the binding affinity, while the Asn-32----His variant could bind to the receptor as well as to the wild-type hEGF. Therefore, it seems to be important for receptor binding that the side chain in position 32 does not have a negative charge but does have an NH group. Thus, we propose that, in the ligand-receptor complex, the receptor recognizes, on one side of the antiparallel beta-sheet structure of hEGF, a wider contact area than previously suggested.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Koide H,Muto Y,Kasai H,Hoshi K,Takusari H,Kohri K,Takahashi S,Sasaki T,Tsukumo K,Miyake T

doi

10.1016/0014-5793(92)80279-p

keywords:

subject

Has Abstract,Author List Incomplete

pub_date

1992-05-04 00:00:00

pages

39-42

issue

1

eissn

0014-5793

issn

1873-3468

journal_volume

302

pub_type

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