Synthetic single domain antibodies for the conformational trapping of membrane proteins.

ABSTRACT: Mechanistic and structural studies of membrane proteins require their stabilization in specific conformations. Single domain antibodies are potent reagents for this purpose, but their generation relies on immunizations, which impedes selections in the presence of ligands typically needed to populate defined conformational states. To overcome this key limitation, we developed an in vitro selection platform based on synthetic single domain antibodies named sybodies. To target the limited hydrophilic surfaces of membrane proteins, we designed three sybody libraries that exhibit different shapes and moderate hydrophobicity of the randomized surface. A robust binder selection cascade combining ribosome and phage display enabled the generation of conformation-selective, high affinity sybodies ag

SUBMITTER: Zimmermann I 

PROVIDER: S-EPMC5967865 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature