Molecular basis for the evolution of species-specific hemoglobin capture by pathogenic Staphylococcus

Jacob E. Choby; Hanna B. Buechi; Allison J. Farrand; Eric P. Skaar; Matthew F. Barber

The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. Closer examination of the Q162R-S170T region of IsdB NEAT1 revealed variation between 227 related staphylococci, but no variation in the critical heme-binding region of NEAT2 ( Figure 6A ). This 228 region of NEAT1 closely interacts with the N-terminal helices of either α-globin and β-globin, in close 229 proximity to both discrete sites bearing signatures of adaptive evolution in α-globin and β-globin ( Figure 230 6B). To determine the functional consequences of variation in this NEAT1 domain, Q162 and S170T 231 were mutagenized in S. aureus IsdB to mimic the sequence of S. schweitzeri and S. argenteus. Variations 232 at both of these positions reduced affinity for human hemoglobin, showing that in the context of S. aureus 233 IsdB, Q162 and S170 are required for high affinity hemoglobin binding ( Figure 6C ). 234 235 All rights reserved. No reuse allowed without permission.