Analysis of human alpha globin gene mutations that impair binding to the alpha hemoglobin stabilizing protein.

ABSTRACT: Alpha hemoglobin stabilizing protein (AHSP) reversibly binds nascent alpha globin to maintain its native structure and facilitate its incorporation into hemoglobin A. Previous studies indicate that some naturally occurring human alpha globin mutations may destabilize the protein by inhibiting its interactions with AHSP. However, these mutations could also affect hemoglobin A production through AHSP-independent effects, including reduced binding to beta globin. We analyzed 6 human alpha globin variants with altered AHSP contact surfaces. Alpha globin amino acid substitutions H103Y, H103R, F117S, and P119S impaired interactions with both AHSP and beta globin. These mutations are destabilizing in biochemical assays and are associated with microcytosis and anemia in humans. By contrast, K99E a

SUBMITTER: Yu X 

PROVIDER: S-EPMC2700329 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature