Biochemistry, structure, and cellular internalization of a four nanobody-bearing Fc dimer.

Protein Science : a Publication of the Protein Society
Eric ChabrolCatherine Vénien-Bryan

Abstract

VHH stands for the variable regions of heavy chain only of camelid IgGs. The VHH family forms a set of interesting proteins derived from antibodies that maintain their capacity to recognize the antigen, despite their relatively small molecular weight (in the 12,000 Da range). Continuing our exploration of the possibilities of those molecules, we chose to design alternative molecules with maintained antigen recognition, but enhanced capacity, by fusing four VHH with one Fc, the fragment crystallizable region of antibodies. In doing so, we aimed at having a molecule with superior quantitative antigen recognition (×4) while maintaining its size below the 110 kDa. In the present paper, we described the building of those molecules that we coined VHH2 -Fc-VHH2 . The structure of VHH2 -Fc-VHH2 in complex with HER2 antigen was determined using electronic microscopy and modeling. The molecule is shown to bind four HER2 proteins at the end of its flexible arms. VHH2 -Fc-VHH2 also shows an internalization capacity via HER2 receptor superior to the reference anti-HER2 monoclonal antibody, Herceptin®, and to a simple fusion of two VHH with one Fc (VHH2 -Fc). This new type of molecules, VHH2 -Fc-VHH2 , could be an interesting addition to the...Continue Reading

References

Sep 9, 1992·International Journal of Cancer. Journal International Du Cancer·C MarthG Daxenbichler
Jan 13, 2001·Oncogene·L M Weiner, G P Adams
Jun 5, 2003·Journal of Structural Biology·Joseph A Mindell, Nikolaus Grigorieff
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Jul 25, 2006·Journal of Structural Biology·Guang TangSteven J Ludtke
Sep 21, 2011·Proceedings of the National Academy of Sciences of the United States of America·Benoît-Joseph LaventieDubravka Drabek
Jun 20, 2013·European Journal of Nuclear Medicine and Molecular Imaging·Marta KijankaPaul M P van Bergen En Henegouwen
Dec 31, 2014·Nature Methods·Jianyi YangYang Zhang
Mar 15, 2016·Methods : a Companion to Methods in Enzymology·Jean-Jacques ToulméFrédéric Ducongé
Dec 16, 2016·Expert Opinion on Biological Therapy·Jogender Tushir-Singh
Apr 4, 2017·Acta Crystallographica. Section F, Structural Biology Communications·Catherine Vénien-BryanJean Albert Boutin
May 26, 2017·Biomedicines·Adam C ParslowAndrew M Scott
Nov 22, 2018·Frontiers in Immunology·Rebecca M RichardsRobbie G Majzner
Feb 9, 2019·Analytical and Bioanalytical Chemistry·J-Pablo SalvadorM-Pilar Marco
Mar 10, 2019·Protein Science : a Publication of the Protein Society·Jean A BoutinHubert Vaudry
Jun 9, 2019·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Jichun YangFeng Sun
Aug 11, 2019·Current Pharmaceutical Biotechnology·Miriam DiboLígia C Faccin-Galhardi
Aug 20, 2019·Protein Science : a Publication of the Protein Society·Lucie HartmannJean A Boutin
Nov 5, 2019·Analytical Biochemistry·Eric ChabrolJean A Boutin
Dec 7, 2019·Current Opinion in Biotechnology·Henri De GreveAnn Depicker
Dec 22, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Fadwa OdehSaid I Ismail
Jan 26, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Shruti BakshiAnn Depicker
Feb 11, 2020·Journal of Drug Targeting·Tongtong QiGuimei Lin
Feb 15, 2020·Drugs of Today·A I GraulL Sorbera
Apr 22, 2020·ELife·Paul J Wichgers SchreurJeroen Kortekaas
Nov 2, 2020·Bioorganic & Medicinal Chemistry Letters·Samia A ElseginySameh S M Soliman

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.