Pacifastin, a novel 155-kDa heterodimeric proteinase inhibitor containing a unique transferrin chain.
A 155-kDa proteinase inhibitor, pacifastin, from plasma of the freshwater crayfish, Pacifastacus leniusculus, was found to be composed of two covalently linked subunits. The two subunits are encoded by two different mRNAs, which were cloned and sequenced. The heavy chain of pacifastin (105 kDa) is related to transferrins, containing three transferrin lobes, two of which seem to be active for iron binding. The light chain of pacifastin (44 kDa) is the inhibitory subunit, and has nine cysteine-rich inhibitory domains that are homologous to each other and to low molecular weight proteinase inhibitors isolated from the grasshopper, Locusta migratoria. The nine light chain domains and the Locusta inhibitors share a characteristic cysteine array (Cys-Xaa9-12-Cys-Xaa2-Cys-Xaa-Cys-Xaa6-8-Cys-Xaa4++ +-Cys) distinct from any described proteinase inhibitor family, suggesting that they constitute a new family of proteinase inhibitors. Pacifastin is the first known protein that has combined properties of a transferrin-like molecule and a proteinase inhibitor.
Liang
Z
Z
Department of Physiological Botany, Uppsala University, Villavägen 6, S-752 36 Uppsala, Sweden.
Sottrup-Jensen
L
L
Aspán
A
A
Hall
M
M
Söderhäll
K
K
D000595:Amino Acid Sequence; D000818:Animals; D003400:Astacoidea; D001483:Base Sequence; D003001:Cloning, Molecular; D008969:Molecular Sequence Data; D011480:Protease Inhibitors / Q000737:chemistry* / Q000302:isolation & purification; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification; D017421:Sequence Analysis; D014168:Transferrin / Q000737:chemistry*
D011480:Protease Inhibitors; D011506:Proteins; D014168:Transferrin; C106709:pacifastin