Heme uptake across the outer membrane as revealed by crystal structures of the receptor-hemophore complex

Abstract

Gram-negative bacteria use specific heme uptake systems, relying on outer membrane receptors and excreted heme-binding proteins (hemophores) to scavenge and actively transport heme, To unravel the unknown molecular details involved. we present 3 structures of the Serratia marcescens receptor HasR in complex with its hemophore HasA. The transfer of heme over a distance of 9 A from its high-affinity site in HasA into a site of lower affinity in HasR is coupled with the exergonic complex formation of the 2 proteins. Upon docking to the receptor. 1 of the 2 axial heme coordinations of the hemophore is initially broken. but the position and orientation of the heme is preserved, Subsequently. steric displacement of heme by a receptor residue ruptures the other axial, coordination. leading to heme transfer into the receptor,