Abstract:
:We have constructed 26-amino acid transmembrane proteins that specifically transform cells but consist of only two different amino acids. Most proteins are long polymers of amino acids with 20 or more chemically distinct side-chains. The artificial transmembrane proteins reported here are the simplest known proteins with specific biological activity, consisting solely of an initiating methionine followed by specific sequences of leucines and isoleucines, two hydrophobic amino acids that differ only by the position of a methyl group. We designate these proteins containing leucine (L) and isoleucine (I) as LIL proteins. These proteins functionally interact with the transmembrane domain of the platelet-derived growth factor β-receptor and specifically activate the receptor to transform cells. Complete mutagenesis of these proteins identified individual amino acids required for activity, and a protein consisting solely of leucines, except for a single isoleucine at a particular position, transformed cells. These surprisingly simple proteins define the minimal chemical diversity sufficient to construct proteins with specific biological activity and change our view of what can constitute an active protein in a cellular context.
journal_name
Proc Natl Acad Sci U S Aauthors
Heim EN,Marston JL,Federman RS,Edwards AP,Karabadzhak AG,Petti LM,Engelman DM,DiMaio Ddoi
10.1073/pnas.1514230112subject
Has Abstractpub_date
2015-08-25 00:00:00pages
E4717-25issue
34eissn
0027-8424issn
1091-6490pii
1514230112journal_volume
112pub_type
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