Protein Engineering and Modeling

New proteins and new binding sites in proteins by directed evolution

Research Overview

The general objective of our group is to develop efficient methods to create new proteins and new binding sites in proteins. We use combinatorial biology and directed evolution methods. The general idea is to design large libraries of folded proteins with randomized binding surface. If the library is properly designed and of high diversity it is then possible to select out from the library specific binders for any chosen protein target. These artificial proteins provide new tools for structural biology, cellular biology, nanomaterials and biotechnology developments.

alphaRep sequences are made by concatenation of synthetic microgenes coding for repeats. Each repeats has 31 residues and 6 variable positions (arrows) a) alphaRep are folded as curved solenoïds b) the binding surface results from juxtaposition of variable positions.

alphaReps

 We have designed and assembled large libraries of artificial repeats proteins named aRep. These proteins are made by the repetition of a sequence motif. Each motif has 31 amino-acids and forms two alpha helices and consecutive motifs stacks on each other to form the folded protein. The six  hyper variable positions of each motifs are juxtaposed on the folded protein. All alphaRep have the same general architecture but differs by the number of motifs and by the chemical composition of their binding surface

Research highlights

Tight and specific binders for a large range of unrelated proteins have been selected. 

Specific alphaReps are soluble, efficiently produced, extremely stable.

Topics

team

Philippe MINARD

Group Leader

Professor

Agathe URVOAS-CISSE

Assistant professor

Marie-Béatrice VALERIO-LEPINIEC

Assistant professor

Michel DESMADRIL

Research Director

Jean KANELLOPOULOS

Emeritus Professor

Mumtaz DJANY

Technician

Florian GOURMELON

Research assistant

Agnès MESNEAU

Engineer

Martin DESMET

Master Student

Adrien FLECK 

Graduate student

Jessalyn ROGERS

Visiting Graduate student

Latest publications

Leger, C., et al., Ligand-induced conformational switch in an artificial bidomain protein scaffold.

Sci Rep, 2019. 9(1): p. 1178.

Di Meo, T. et al., Functionalized artificial bi-domain proteins based on an α-solenoid protein repeat scaffold: a new class of artificial Diels-Alderases. ACS omega, 2019. 4 : p. 4437-4447.

Campanacci, V., et al., Selection and Characterization of Artificial Proteins Targeting the Tubulin alpha Subunit. Structure, 2019. 27(3): p. 497-506 e4.

Campanacci, V., et al., Insight into microtubule nucleation from tubulin-capping proteins.

Proc Natl Acad Sci U S A, 2019. 116(20): p. 9859-9864.

Léger C et al Picomolar Biosensing and Conformational Analysis Using Artificial Bidomain Proteins and Terbium-to-Quantum Dot Förster Resonance Energy Transfer.

ACS Nano. 2020 ;14(5):5956-5967.

 

For all the publications of the Team click on the button below.

External funding

Artemis (2015-2017),

Alphasense (2016-2019)

Scaffold –Art (2019-2021)

 Sars-Cov2 Block entry (2020-2021)

DIM1(2019)  health  APRICOT Alpharep libraries for PRion COnformers sTudies

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