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.
Molecular Biophysics Group, SERC Daresbury Laboratory, Warrington, Cheshire, U.K.
J G
JG
Grossmann
A B
AB
Mason
R C
RC
Woodworth
M
M
Neu
P F
PF
Lindley
S S
SS
Hasnain
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