CRYSTALS OF THE AUGMENTOR OF LIVER REGENERATION. C.-K. Wu1,2, J.P. Rose1, A. Francavilla3, J.G. Prelich3, A. Iacobellis3, M. Hagiya4, A. Rao3, T. Starzl3 and B.C. Wang1, 1Dept. of Biochemistery and Molecular Biology, Univ. of Georgia, Athens GA 30602, USA, 2Dept. of Crystallography, Univ. of Pittsburgh, Pittsburgh, PA 15260, USA, 3Pittsburgh Transplant Inst., Univ. of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA and 4Pharmaceuticals Res. Ctr., Toyobo Co. Ltd., Ohtsu, Shiga 520-02, Japan
Almost every school child knows that chameleons can regenerate a lost tail. This interesting phenomenon of regrowth of lost body parts common in lower animals is generally rare in mammals. The liver however, is an unique organ in that it is capable of regeneration.
A new cellular growth factor termed augmentor of liver regeneration (ALR) shown to have a proliferative effect on liver cells while at the same time producing an immunosuppressive effect on liver-resident natural killer cells and liver-resident mononuclear leukocytes has been crystallized. The crystals diffract to beyond 2 Å resolution and belong to space group P212121, with a=35.5Å, b=108.1Å and c=125.1Å. Based on 4 molecules per asymmetric unit, the Matthews coefficient is calculated to be 2.16 Å3/Da which corresponds to a solvent content of 43%.
Rat ALR has two related forms, "short" ALR which has 125 amino acid residues and "long" ALR, (ALR198), which contains 73 additional residues in the N-terminal segment of ALR . The long ALR is the result of an additional inframe ATG initiation site which is 5' to the initiation site used to code the 125 residue protein. The ALR cDNA sequence shows 50% homology with the sequence of the dual-function gene ERV1 (Essential for Respiration and Viability) of "baker's yeast", Saccharomyces cerevisiae. The ERV1 gene products are part of the mitochondrial respiratory chain, are essential for oxidative phosphorlyation and vegetative growth and also play a critical role in cell growth and regulation. Deletion of this gene has been shown to cause a severe growth defect and irreversible cessation of cell division after 3-4 days. The ALR gene could represent the mammalian equivalent of the ERV1 gene.
Details of the structure analysis will be presented.