The platelet integrin ␣ IIb ␤ 3 mediates platelet aggregation and platelet adhesion. This integrin is the key to hemostasis and also to pathologic vascular occlusion. A key domain on ␣ IIb ␤ 3 is the ligand binding site, which can bind to plasma fibrinogen and to a number of ArgGly-Asp (RGD)-type ligands. However, the nature and function of the ligand binding pocket on ␣ IIb ␤ 3 remains controversial. Some studies suggest the presence of two ligand binding pockets, whereas other reports indicate a single binding pocket. Here we use surface plasmon resonance to show that ␣ IIb ␤ 3 contains two distinct ligand binding pockets. One site binds to fibrinogen, and a separate site binds to RGD-type ligands. More importantly, however, the two ligand binding pockets are interactive. RGD-type ligands are capable of binding to ␣ IIb ␤ 3 even when it is already occupied by fibrinogen. Once bound, RGD-type ligands induce the dissociation of fibrinogen from ␣ IIb ␤ 3 . This allosteric cross-talk has important implications for anti-platelet therapy because it suggests a novel approach for the dissolution of existing platelet thrombi.

There are four groups of RNA bacteriophages with distinct antigenic and physicochemical properties due to differences in surface residues of the viral coat proteins. Coat proteins also play a role as translational repressor during the viral life cycle, binding an RNA hairpin within the genome. In this study, the first crystal structure of the coat protein from a Group I1 phage GA is reported and compared to the Group I MS2 coat protein. The structure of the GA dimer was determined at 2.8 8, resolution (R-factor = 0.20). The overall folding pattern of the coat protein is similar to the Group I MS2 coat protein in the intact virus (Golmohammadi R, Valegird K, Fridborg K, Liljas L, 1993, J Mol Biol234:620-639) or as an unassembled dimer (Ni CZ, Syed R, Kodandapani R, Wickersham J, Peabody DS, Ely KR, 1995, Srructure 3:255-263). The structures differ in the FG loops and in the first turn of the a A helix. GA and MS2 coat proteins differ in sequence at 49 of 129 amino acid residues. Sequence differences that contribute to distinct immunological and physical properties of the proteins are found at the surface of the intact virus in the AB and FG loops. There are six differences in potential RNA contact residues within the RNA-binding site located in an antiparallel @sheet across the dimer interface. Three differences involve residues in the center of this concave site: Lys/Arg 83, Ser/Asn 87, and Asp/Glu 89. Residue 87 was shown by molecular genetics to define RNA-binding specificity by GA or MS2 coat protein (Lim F, Spingola M, Peabody DS, 1994, J BioZ Chem 269:9006-9010). This sequence difference reflects recognition of the nucleotide at position -5 in the unpaired loop of the translational operators bound by these coat proteins. In GA, the nucleotide at this position is a purine whereas in MS2, it is a pyrimidine.Keywords: bacteriophage coat protein; crystal structure; RNA hairpin; translational repressor; virus RNA bacteriophages are small viruses with a simple organization. These viruses have an icosahedral shell composed of 180 copies of coat protein and one copy of the maturation protein that encapsidate genomic RNA ,which is approximately 3,500 nucleotides in length. The single-stranded RNA genome also acts as mRNA, encoding four proteins: the viral coat protein, a maturation protein, a replicase subunit, and the lysis protein. These phages were first isolated from Escherichia coli, but later were also found in Caulobacter and Pseudomonas. To date, the coliphages have been the best studied and are classified into four groups based on serological and physicochemical properties. Groups I and I1 are quite similar, with MS2 and GA phages being the well-characterized members of these groups. Phages Q p and SP, members of Groups I11 and IV, respectively, are more divergent from Groups I and 11.

Abstract:Fibronectin is a large cell adhesion molecule that is composed of several functional domains. The cell-binding domain that binds to cell surface integrins consists of repeated homologous type 111 modules. In this study, recombinant fragments from the cell-binding domain of human fibronectin that participate in a newly characterized fibronectin-fibronectin interaction with FNIII I were crystallized. In each case, the crystals had more than one fibronectin fragment in the asymmetric unit. Crystals of F N I I I l o~l , grew in the space group C2 with a = 117.1 A, b = 38.6 A, c = 80.6 A, /3 = 97.2", and two molecules in the asymmetric unit.These crystals diffracted to 2.5 8, resolution. Fragment FNIII,-, and a shorter fragment, FNIIIx-,o, crystallized in hexagonal space groups with large unit cells and two to four molecules per asymmetric unit. Even very large crystals of these fragments did not diffract beyond 4 A. The crystal packing for this collection of fibronectin fragments suggests conformational flexibility between linked type 111 modules. The functional relevance of this flexibility for elongated versus compact models of the cell-binding domain of fibronectin is discussed.

The Natural Gas Policy Act of 1978 (NGPA), is frequently accorded the dubious distinction of being the most complex, ambiguous, and internally inconsistent piece of legislation ever passed by Congress. This paper will take a brief look at the history of natural gas pricing policy, analyze the ways in which the NGPA fits into this historical perspective, discuss the achievements and shortcomings of that statute and speculate about the future of natural gas regulation. Few would disagree that from a standpoint of economic efficiency and public policy decontrol of at least new natural gas is warranted. The simple fact is that if the price level for natural gas is kept artificially low, there will be less natural gas produced than the demand for it. Despite what is coming to be an increasing perception that deregulation would be generally beneficial, the NGPA fell far short of the ultimate goal of deregulation. In order to understand why political reality has not kept pace with economic reality it would be helpful to briefly consider the history of natural gas regulation. In 1954 the Supreme Court extended FPC regulation to the wellhead price of natural gas sold for resale in interstate commerce.1/ During the seven years following the Phillips decision there was little indication of a disequilibrium in the supply and demand of natural gas. Indeed, during the 1950's the supply of natural gas continued to increase as it had since World War II and increase dramatically. During this period, natural gas was still largely a by-product of the exploration for and production of oil, so that the relative availability of gas was not dramatically affected by federal price controls. Although economists and the gas industry at times raised dire forewarnings of the longterm adverse effects of price control, the immediate, practical effect did not appear particularly severe.