Synthetic integrin antibodies discovered by yeast display reveal αV subunit pairing preferences with β subunits

Integrins are cell surface receptors that mediate the interactions of cells with their surroundings and play essential roles in cell adhesion, migration, and homeostasis. Eight of the 24 integrins bind to the tripeptide Arg-Gly-Asp (RGD) motif in their extracellular ligands, comprising the RGD-bindi...

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Main Authors: Yuxin Hao (Author), Jiabin Yan (Author), Courtney Fraser (Author), Aiping Jiang (Author), Murali Anuganti (Author), Roushu Zhang (Author), Kenneth Lloyd (Author), Joseph Jardine (Author), Jessica Coppola (Author), Rob Meijers (Author), Jing Li (Author), Timothy A. Springer (Author)
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Published: Taylor & Francis Group, 2024-12-01T00:00:00Z.
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042 |a dc 
100 1 0 |a Yuxin Hao  |e author 
700 1 0 |a Jiabin Yan  |e author 
700 1 0 |a Courtney Fraser  |e author 
700 1 0 |a Aiping Jiang  |e author 
700 1 0 |a Murali Anuganti  |e author 
700 1 0 |a Roushu Zhang  |e author 
700 1 0 |a Kenneth Lloyd  |e author 
700 1 0 |a Joseph Jardine  |e author 
700 1 0 |a Jessica Coppola  |e author 
700 1 0 |a Rob Meijers  |e author 
700 1 0 |a Jing Li  |e author 
700 1 0 |a Timothy A. Springer  |e author 
245 0 0 |a Synthetic integrin antibodies discovered by yeast display reveal αV subunit pairing preferences with β subunits 
260 |b Taylor & Francis Group,   |c 2024-12-01T00:00:00Z. 
500 |a 10.1080/19420862.2024.2365891 
500 |a 1942-0870 
500 |a 1942-0862 
520 |a Integrins are cell surface receptors that mediate the interactions of cells with their surroundings and play essential roles in cell adhesion, migration, and homeostasis. Eight of the 24 integrins bind to the tripeptide Arg-Gly-Asp (RGD) motif in their extracellular ligands, comprising the RGD-binding integrin subfamily. Despite similarity in recognizing the RGD motif and some redundancy, these integrins can selectively recognize RGD-containing ligands to fulfill specific functions in cellular processes. Antibodies against individual RGD-binding integrins are desirable for investigating their specific functions, and were selected here from a synthetic yeast-displayed Fab library. We discovered 11 antibodies that exhibit high specificity and affinity toward their target integrins, i.e. αVβ3, αVβ5, αVβ6, αVβ8, and α5β1. Of these, six are function-blocking antibodies and contain a ligand-mimetic R(G/L/T)D motif in their CDR3 sequences. We report antibody-binding specificity, kinetics, and binding affinity for purified integrin ectodomains, as well as intact integrins on the cell surface. We further used these antibodies to reveal binding preferences of the αV subunit for its 5 β-subunit partners: β6 = β8 > β3 > β1 = β5. 
546 |a EN 
690 |a RGD-binding integrin 
690 |a yeast display 
690 |a antibody screening 
690 |a inhibitory antibody 
690 |a function blocking 
690 |a Therapeutics. Pharmacology 
690 |a RM1-950 
690 |a Immunologic diseases. Allergy 
690 |a RC581-607 
655 7 |a article  |2 local 
786 0 |n mAbs, Vol 16, Iss 1 (2024) 
787 0 |n https://www.tandfonline.com/doi/10.1080/19420862.2024.2365891 
787 0 |n https://doaj.org/toc/1942-0862 
787 0 |n https://doaj.org/toc/1942-0870 
856 4 1 |u https://doaj.org/article/cf98f9e736e742c0b512e4f1ef781a2c  |z Connect to this object online.