Rous sarcoma virus structure

In the structure of the apo-form of HIV PR, the flaps from both monomers are related by crystallographic two-fold symmetry and can be considered as being in an open conformation. In the structures of related proteases from Rous Sarcoma Virus and HIV-2, the flaps are either crystallographically disordered or in a partly closed conformation [18]. This suggests that, in solution, in the absence of ligands, the flaps are rather flexible and that the stable conformation of the flaps observed in the crystal structure of the apo-enzyme of HIV PR could be considered to result from kinetic trapping during the crystallization process. 

Leis, J., Weber, L, Wlodawer, A., and Skalka, A.M. (1990). Structure-function analysis of the Rous sarcoma virus-specific proteinase. ASM News 56, 77 81. 

Retroviruses encode a protease (PR) responsible for cleaving polyprotein precursors, and such processing is essential for proper virion assembly and maturation. Based on the presence of a sequence Asp-Ser/Thr-Gly in the active sites of retroviral proteases (1) and their inhibition in vitro by pepstatin (2-7), these enzymes have been classified as members of the aspartic protease family. Crystal structures have been determined for the proteases from Rous sarcoma virus (RSV PR) (8), from two variants and several mutants of the human immunodeficiency vims (HIV PR) (9-11), from feline immunodeficiency virus (FIV PR) (12) and from equine infectious anemia vims (EIAV PR) (13). Aspartic proteases contain a single active site which includes two aspartates. In apoenzymes, the two catalytic Asp residues from the active site triad have been found to be in hydrogen bond contact with a water molecule (10). Mutations of the active site Asp25 in HIV-1 PR into Asn (14,15), Thr (3) or Ala (4,16,17) led to an inactive enzyme. Similarly, the RSV PR was inactivated by mutation of its active site Asp to He (18). 

Binding of phosphotyrosine 527 to the SH2 domain induces conformational strains in the SH3 and kinase domains, distorting the kinase active site so it is catalytically inactive. The kinase activity of cellular Src proteins is normally activated by removing the phosphate on tyrosine 527. (b) Domain structure of c-Src and v-Sre. Phosphorylation of tyrosine 527 by Csk, another cellular tyrosine kinase, inactivates the Src kinase activity. The transforming v-Src oncoprotein encoded by Rous sarcoma virus is missing the C-terminal 18 amino acids including tyrosine 527 and thus is constitutively active. [Part (a) from F. Sicheri et al.,... 

Fig. 16.2. A section of the alignment of sequences of aspartic proteinases achieved by comparing the three-dimensional structures using COMPARER [14]. HIV human immunodeficiency virus RSV Rous sarcoma virus APE endothiapepsin APP penicillopepsin APR rhizopuspepsin PEP hexagonal porcine pepsin CHY calf chymosin. The last letter refers to the amino (N) or car-boxy (C) terminal domains of the pepsins. The coordinates of the three-dimensional structures were obtained from the PDB databank [24]. The amino acid code is the standard one-letter code (see Appendix C) formatted using the following conventions [7] ...

One of the domains of the receptor containing a phosphotyrosine residue forms a binding site for intracellular proteins with a specific three-dimensional structure known as the SH2 domain (the Src homology 2 domain, named for the first protein in which it was found, the src protein of the Rous sarcoma virus). The adaptor... 

Kitamura, N. Kitamura, A. Toyoshima, K. Hirayama, Y. Yoshida, M. Avian sarcoma virus Y73 genome sequence and structural similarity of its transforming gene product to that of Rous sarcoma virus. Nature, 297, 205-208 (1982)... 

A major group of glycoproteins, which have a high molecular weight and stain only faintly with Coomassie Blue, but bind to concanavalin A, have been identified in the plasma membranes of Chinese hamster fibroblasts. Their presence is only revealed by two-dimensional electrophoresis and not by conventional electrophoretic techniques. The alteration of membrane components of hamster-kidney fibroblasts transformed by Rous sarcoma virus is expressed in an increase in the levels of three glycoproteins, when compared with.those of control cells. The structure (24) of the major cell-surface glycoprotein from hamster-embryo fibroblasts has been established. ... 

An L-fucose-deficient, precursor glycoprotein of Rauscher leukaemia virus glycoprotein (69/71) has been reported it is synthesized in virus-infected cells from a glycoprotein (mol. wt. 9 x 10 ) which can be labelled with radioactive 2-amino-2-deoxy-D-glucose, but not with L-fucose, whereas the Rauscher glycoprotein can be labelled with both. The principal glycoprotein in three strains of Rous sarcoma virus has been purified, and the structures (1) and (2) were proposed for the carbohydrate moieties of the subgroups A and B, respectively. ... 

Cell-surface structure and function in Rous sarcoma virus-transformed cells, in Biogenesis and Turnover of Membrane Macromolecules (J. S. Cook, ed.), pp. 251-276, Raven Press, New York. 

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