Structural insights into the function-modulating effects of nanobody binding to the integrin receptor α_Mβ₂.

ABSTRACT: The integrin receptor α_Mβ₂ mediates phagocytosis of complement-opsonized objects, adhesion to the extracellular matrix, and transendothelial migration of leukocytes. However, the mechanistic aspects of α_Mβ₂ signaling upon ligand binding are unclear. Here, we present the first atomic structure of the human α_Mβ₂ headpiece fragment in complex with the nanobody (Nb) hCD11bNb1 at a resolution of 3.2 Å. We show that the receptor headpiece adopts the closed conformation expected to exhibit low ligand affinity. The crystal structure indicates that in the R77H α_M variant, associated with systemic lupus erythematosus, the modified allosteric relationship between ligand binding and integrin outside-inside signaling is due to

SUBMITTER: Jensen RK 

PROVIDER: S-EPMC9287160 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature