Dataset Information

Mls-1 is encoded by the long terminal repeat open reading frame of the mouse mammary tumor provirus Mtv-7.

ABSTRACT: The murine Mls-1 antigen is the prototype of endogenous superantigens, molecules whose activities lead to deletion of T cells expressing certain T-cell receptor V beta genes from the mature repertoire. However, Mls-1 also stimulates T cells expressing these particular V beta genes (V beta 6, V beta 7, V beta 8.1, and V beta 9) in vitro, making it one of the strongest known T-cell activators. We have recently reported that the Mls-1 gene is closely linked to the endogenous mammary tumor virus Mtv-7. We now demonstrate that Mls-1 is encoded by the open reading frame in the U3 region of the long terminal repeat of Mtv-7. However, control of expression of this molecule seems complex, depending on the promoter used for the transfection experiments. The sequence of the Mtv-7 open reading frame differs from all other known mammary tumor virus open reading frame sequences in the 3' end, suggesting that the T-cell receptor V beta specificity is conferred by the C terminus of the molecule. The predicted structure of the protein encoded by the open reading frame is consistent with a type II transmembrane molecule where the C terminus is extracellular.

SUBMITTER: Beutner U

PROVIDER: S-EPMC49306 | biostudies-other | 1992 Jun

REPOSITORIES: biostudies-other

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Mls-1 is encoded by the long terminal repeat open reading frame of the mouse mammary tumor provirus Mtv-7.

Beutner U U Frankel W N WN Cote M S MS Coffin J M JM Huber B T BT

Proceedings of the National Academy of Sciences of the United States of America 19920601 12

The murine Mls-1 antigen is the prototype of endogenous superantigens, molecules whose activities lead to deletion of T cells expressing certain T-cell receptor V beta genes from the mature repertoire. However, Mls-1 also stimulates T cells expressing these particular V beta genes (V beta 6, V beta 7, V beta 8.1, and V beta 9) in vitro, making it one of the strongest known T-cell activators. We have recently reported that the Mls-1 gene is closely linked to the endogenous mammary tumor virus Mtv ...[more]

PMID: 1319061

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Project description:Herpesviruses alternate between the latent and the lytic life cycle. Switching into the lytic life cycle is important for herpesviral replication and disease pathogenesis. Activation of a transcription factor replication and transcription activator (RTA) has been demonstrated to govern this switch in Kaposi's sarcoma-associated herpesvirus (KSHV). The protein encoded by open reading frame 49 from KSHV (ORF49KSHV) has been shown to upregulate lytic replication in KSHV by enhancing the activities of the RTA. We have solved the crystal structure of the ORF49KSHV protein to a resolution of 2.4 Å. The ORF49KSHV protein has a novel fold consisting of 12 alpha-helices bundled into two pseudodomains. Most notably are distinct charged patches on the protein surface, which are possible protein-protein interaction sites. Homologs of the ORF49KSHV protein in the gammaherpesvirus subfamily have low sequence similarities. Conserved residues are mainly located in the hydrophobic regions, suggesting that they are more likely to play important structural roles than functional ones. Based on the identification and position of three sulfates binding to the positive areas, we performed some initial protein-DNA binding studies by analyzing the thermal stabilization of the protein in the presence of DNA. The ORF49KSHV protein is stabilized in a dose-responsive manner by double-stranded oligonucleotides, suggesting actual DNA interaction and binding. Biolayer interferometry studies also demonstrated that the ORF49KSHV protein binds these oligonucleotides. Kaposi's sarcoma-associated herpesvirus (KSHV) is a tumorigenic gammaherpesvirus that causes multiple cancers and lymphoproliferative diseases. The virus exists mainly in the quiescent latent life cycle, but when it is reactivated into the lytic life cycle, new viruses are produced and disease symptoms usually manifest. Several KSHV proteins play important roles in this reactivation, but their exact roles are still largely unknown. In this study, we report the crystal structure of the open reading frame 49 protein encoded by KSHV (ORF49KSHV). Possible regions for protein interaction that could harbor functional importance were found on the surface of the ORF49KSHV protein. This led to the discovery of novel DNA binding properties of the ORF49KSHV protein. Evolutionary conserved structural elements with the functional homologs of ORF49KSHV were also established with the structure.

Dataset Information

Mls-1 is encoded by the long terminal repeat open reading frame of the mouse mammary tumor provirus Mtv-7.

Publications

Mls-1 is encoded by the long terminal repeat open reading frame of the mouse mammary tumor provirus Mtv-7.

Similar Datasets

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