Determinants of the assembly and function of antibody variable domains.

ABSTRACT: The antibody Fv module which binds antigen consists of the variable domains V_L and V_H. These exhibit a conserved ß-sheet structure and comprise highly variable loops (CDRs). Little is known about the contributions of the framework residues and CDRs to their association. We exchanged conserved interface residues as well as CDR loops and tested the effects on two Fvs interacting with moderate affinities (K_Ds of ~2.5 µM and ~6 µM). While for the rather instable domains, almost all mutations had a negative effect, the more stable domains tolerated a number of mutations of conserved interface residues. Of particular importance for Fv association are V_LP44 and V_HL45. In general, the exchange of conserved residues in the V_L/V_H

SUBMITTER: Herold EM 

PROVIDER: S-EPMC5613017 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature