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Title: Identification of two amino acids in activin A that are important for biological activity and binding to the activin type II receptors
Authors: Wuytens, Gunther
Verschueren, K
de Winter, J P
Gajendran, N
Beek, Lisette
Devos, Kristien
Bosman, F
De Waele, Peter
Andries, Maria
van den Eijnden-van Raaij, A J
Smith, J C
Huylebroeck, Danny #
Issue Date: Apr-1999
Series Title: Journal of Biological Chemistry vol:274 issue:14 pages:9821-7
Abstract: Activins are members of the transforming growth factor-beta family of growth and differentiation factors. In this paper, we report the results of a structure-function analysis of activin A. The primary targets for directed mutagenesis were charged, individual amino acids located in accessible domains of the protein, concentrating on those that differ from transforming growth factor-beta2, the x-ray crystal structure of which is known. Based on the activities of the recombinant activin mutants in two bioassays, 4 out of 39 mutant proteins (D27K, K102A, K102E, and K102R) produced in a vaccinia virus system were selected for further investigation. After production in insect cells and purification of these four mutants to homogeneity, they were studied in bioassays and in cross-linking experiments involving transfected receptor combinations. Mutant D27K has a 2-fold higher specific bio-activity and binding affinity to an ActRIIA/ALK-4 activin receptor complex than wild type activin, whereas mutant K102E had no detectable biological activity and did not bind to any of the activin receptors. Mutant K102R and wild type activin bound to all the activin receptor combinations tested and were equipotent in bioassays. Our results with the Lys-102 mutants indicate that the positive charge of amino acid 102 is important for biological activity and type II receptor binding of activins.
URI: 
ISSN: 0021-9258
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Pharmacology Section (-)
Molecular Biology (Celgen) (-)
Laboratory of Biosignaling & Therapeutics
# (joint) last author

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