Existence of a noncanonical state of iron-bound transferrin at endosomal pH revealed by hydrogen exchange and mass spectrometry.

ABSTRACT: Transferrin (Tf) is an enigmatic metalloprotein that exhibits a profound conformational change upon binding of ferric ion and a synergistic anion (oxalate or carbonate). While the apo and holo forms of the protein have well-defined and stable conformations termed "open" and "closed," certain aspects of Tf behavior imply the existence of alternative protein states. In this work, hydrogen/deuterium exchange was used in combination with mass spectrometry to map solvent-accessible surfaces of the iron-bound and iron-free forms of the N-terminal lobe of human serum Tf at both neutral and endosomal pH levels. While the deuterium uptake is significantly decelerated in the iron-bound state of the protein (compared with the apo form) at neutral pH, the changes are distributed very unevenly across t

SUBMITTER: Bobst CE 

PROVIDER: S-EPMC2933096 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature