Asp ligand provides the trigger for closure of transferrin molecules. Direct evidence from X-ray scattering studies of site-specific mutants of the N-terminal half-molecule of human transferrin.
Recent X-ray crystallographic and solution X-ray scattering studies have shown that transferrins (serum transferrin, lactoferrin and ovotransferrin) undergo a major conformational change when iron is incorporated into the molecule. Apo-proteins show a structure with open interdomain clefts which close when iron is bound. The closed conformation has been suggested as an important step in the receptor recognition. Here, we report X-ray solution scattering experiments of the mutated N-terminal fragment of human serum transferrin with Asp63-->Ser (Cys). The data provide the first direct experimental evidence for the existence of a trigger mechanism for the closure of the interdomain cleft and that this trigger mechanism is disrupted by mutation of Asp63, the only ligand of iron from domain I.
Grossmann
J G
JG
Molecular Biophysics Group, SERC Daresbury Laboratory, Warrington, Cheshire, U.K.
Mason
A B
AB
Woodworth
R C
RC
Neu
M
M
Lindley
P F
PF
Hasnain
S S
SS
D001224:Aspartic Acid / Q000378:metabolism*; D006801:Humans; D006860:Hydrogen Bonding; D007501:Iron / Q000378:metabolism; D008024:Ligands; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D012542:Scattering, Radiation; D014168:Transferrin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014965:X-Rays
D008024:Ligands; D014168:Transferrin; D001224:Aspartic Acid; D007501:Iron