AlphaRep

SELECTION OF ARTIFICIAL BINDERS (ALPHAREP)

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Presentation

We have designed and assembled a large library of artificial repeats proteins named alphaRep (1). AlphaRep proteins binding tightly and specifically any predefined folded protein can be selected out from this library (2). AlphaRep generation does not require animal immunization and gives rise to renewable, sequence defined, binders. Specific alphaReps are soluble, efficiently produced, disulfide-free and extremely stable. These artificial proteins can be easily modified (fusion, dimerisation, incorporation of fluorophores, tracers, etc.).

AlphaReps can be used as protein tools in various contexts:

  • Structural biology (crystallization helpers, electron microscopy platforms) Upon binding, alphaRep can stabilize their specific partners, and provide a large external surface able to generate intermolecular contacts, and favor crystallization (3). Crystal structures of complexes between proteins and their cognate alphaRep have been obtained including for proteins difficult to crystallize when isolated (4).
  • Antiviral nanoligands: Specific binders targeting the SARS-CoV2 spike protein were selected from the αRep library. Two combined αRep nanoligands neutralize SARS-CoV-2 variants and reduce infection severity in hamster (5).
  • Specific recognition unit for cellular applications like targeted protein degradation (PROTAC) (6).
References

Urvoas A, Guellouz A, Valerio-Lepiniec M, Graille M, Durand D, et al. 2010. J Mol Biol 404: 307-27

  1. Guellouz A, Valerio-Lepiniec M, Urvoas A, Chevrel A, Graille M, et al. 2013. PLoS One 8: e71512
  2. Chevrel A, Mesneau A, Sanchez D, Celma L, Quevillon-Cheruel S, et al. 2018. J Struct Biol 201: 88-99
  3. Campanacci V, Urvoas A, Consolati T, Cantos-Fernandes S, Aumont-Nicaise M, et al. 2019. Structure 27: 497-506 e4
  4. Thébault S. Lejal N., Dogliani A., Donchet A., Urvoas A., Valerio-Lepiniec M, et al. 2022, PLoS Pathog 18(9): e1010799.
  5. Lim S, Khoo R, Peh KM, Teo J, Chang SC, et al. 2020. Proc Natl Acad Sci U S A117: 5791-800

Service and activity

The platform offers generation and production of artificial proteins (alphaRep) that bind with high affinity and specificity any chosen protein target.

Platform users can participate to the experimental process for the selection of binders following a training period

Academic projects are considered as collaborations. Only consumable fees and real costs of the project are invoiced. Financial supports can be required conjointly from different agencies (local, regional or national infrastructures…)

If molecules derived from the project give rise to publication, or any other valorization format, the platform staff involved in the project will be cited as co-authored

Contacts

If you have a project, do not hesitate to contact the researchers of the alphaRep facility:

Agathe Urvoas                        agathe.urvoas@i2bc.paris-saclay.fr

Marielle Valerio-Lepiniec      marielle.valerio@i2bc.paris-saclay.fr

Philippe Minard                      philippe.minard@i2bc.paris-saclay.fr

team

Agathe URVOAS

Head of Facility

Researcher

Marielle VALERIO-LEPINIEC

Researcher

Philippe MINARD

Researcher

Justine DUWER

Engineer

Certifications and Networks

The alphaRep facility is labeled by French infrastructures for structural biology:

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