Unique mechanisms to increase structural stability and enhance antigen binding in nanobodies.

 0 Người đánh giá. Xếp hạng trung bình 0

Tác giả: Steven C Almo, Jeffrey B Bonanno, Marc Brillantes, Brian T Chait, Peter C Fridy, Natalia E Ketaren, Vladimir Malashkevich, Deena A Oren, Michael P Rout, Andrej Šali, Tanmoy Sanyal, Mary K Thompson

Ngôn ngữ: eng

Ký hiệu phân loại: 623.447 Destructive vibration weapons

Thông tin xuất bản: United States : Structure (London, England : 1993) , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 680151

Nanobodies are single domain antibody variants proving themselves to be compelling tools for research, disease diagnostics, and as therapeutics targeting a myriad of disease agents. However, despite this potential, their mechanisms of paratope presentation and structural stabilization have not been fully explored. Here, we show that unlike monoclonal antibodies, a nanobody repertoire maximizes sampling of an antigen surface by binding a single antigen in at least three different orientations, which are correlated with their paratope composition. Structure-guided reengineering of several nanobodies reveals that a single point mutation within the paratope or a highly conserved region of a nanobody's framework 3 (FR3) can markedly improve antigen affinity, nanobody stability, or both. Conversely, we show the negative impact on antigen affinity when "over-stabilizing" nanobodies. Collectively our results provide a universal strategy to tune a nanobody's affinity by modifying specific residues that can readily be applied to guide nanobody optimization and functionalization.
Tạo bộ sưu tập với mã QR

THƯ VIỆN - TRƯỜNG ĐẠI HỌC CÔNG NGHỆ TP.HCM

ĐT: (028) 36225755 | Email: tt.thuvien@hutech.edu.vn

Copyright @2024 THƯ VIỆN HUTECH