Activation of the HTLV‐I promoter by the viral Tax1 transactivator is mediated by a 21 bp sequence motif imperfectly repeated three times and composed of three exactly conserved domains (A, B and C from 5′ to 3′). We show here that the Tax1 response requires the integrity of the B domain and of at least one of the flanking A or C domains. We have identified three cellular proteins which bind specifically to the 21 bp motif. One of these is the already well‐characterized transcription factor ATF. The other two, namely HEB1 and HEB2, are specific for the 21 bp motif. HEB1 can bind to either domain A or C, but binding of ATF and HEB2 is determined by domain B. However, neither domain B alone, nor ATF/CREB binding sites respond significantly to Tax1. We therefore propose that Tax1 induction of the 21 bp enhancer element requires interaction with the two different cellular proteins identified in this study: HEB1 and HEB2, rather than binding of the ATF factor.

The crystal structure of the ternary porcine lipasecolipase-tetra ethylene glycol monooctyl ether (TGME) complex has been determined at 2.8 Å resolution. The crystals belong to the cubic space group F23 with a ‫؍‬ 289.1 Å and display a strong pseudo-symmetry corresponding to a P23 lattice. Unexpectedly, the crystalline two-domain lipase is found in its open configuration. This indicates that in the presence of colipase, pure micelles of the nonionic detergent TGME are able to activate the enzyme; a process that includes the movement of an N-terminal domain loop (the flap). The effects of TGME and colipase have been confirmed by chemical modification of the active site serine residue using diisopropyl p-nitrophenylphosphate (E600). In addition, the presence of a TGME molecule tightly bound to the active site pocket shows that TGME acts as a substrate analog, thus possibly explaining the inhibitory effect of this nonionic detergent on emulsified substrate hydrolysis at submicellar concentrations. A comparison of the lipase-colipase interactions between our porcine complex and the human-porcine complex (van Tilbeurgh, H., Egloff, M.-P., Martinez, C., Rugani, N., Verger, R., and Cambillau, C. (1993) Nature 362, 814 -820) indicates that except for one salt bridge interaction, they are conserved. Analysis of the superimposed complexes shows a 5.4°rotation on the relative position of the N-terminal domains excepting the flap that moves in a concerted fashion with the C-terminal domain. This flexibility may be important for the binding of the complex to the water-lipid interface.Pancreatic lipase (triacylglycerol acylhydrolase, EC 3.1.1.3) plays a key role in dietary fat absorption in the intestine. It converts insoluble long chain triglycerides into more polar molecules that are able to cross the brush border membrane of enterocytes as mixed micelles with bile salts. Besides their role in triglyceride digestion through lipid emulsification and intestinal fat absorption, bile salts exert a strong inhibitory effect by preventing lipase adsorption through coating of the water-lipid interface (1). Lipase adsorption is a fundamental process because the enzyme catalyzes a heterogeneous reaction that involves an interfacial activation step. To counteract the inhibitory effect of bile salts, the pancreas secretes a small protein, colipase (molecular mass, 10 kDa), which anchors lipase to the bile salt-coated water-lipid interface in their presence (2, 3). Thus, lipolysis results from the combined effect of pancreatic lipase, colipase, and bile salts.Pancreatic lipase is a single polypeptide chain of 50 kDa. This protein has been characterized in several species, and the amino acid sequences of the enzyme from pig, man, horse, rabbit, rat, guinea pig, and coypu (4 -10) have been reported. In addition, related lipases (type 1 and 2) have been found in dog, rat man, guinea pig, and coypu (11-16) by screening pancreatic cDNA libraries. The localization and role of these related lipases is not clear.Crystal structures of the human ...

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