Biologically active LIL proteins built with minimal chemical diversity.

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.

authors

Heim EN,Marston JL,Federman RS,Edwards AP,Karabadzhak AG,Petti LM,Engelman DM,DiMaio D

doi

10.1073/pnas.1514230112

subject

Has Abstract

pub_date

2015-08-25 00:00:00

pages

E4717-25

issue

34

eissn

0027-8424

issn

1091-6490

pii

1514230112

journal_volume

112

pub_type

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