1jsg
From Proteopedia
(New page: 200px<br /> <applet load="1jsg" size="450" color="white" frame="true" align="right" spinBox="true" caption="1jsg, resolution 2.50Å" /> '''CRYSTAL STRUCTURE O...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1jsg.gif|left|200px]]<br /> | + | [[Image:1jsg.gif|left|200px]]<br /><applet load="1jsg" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1jsg" size=" | + | |
caption="1jsg, resolution 2.50Å" /> | caption="1jsg, resolution 2.50Å" /> | ||
'''CRYSTAL STRUCTURE OF P14TCL1, AN ONCOGENE PRODUCT INVOLVED IN T-CELL PROLYMPHOCYTIC LEUKEMIA, REVEALS A NOVEL B-BARREL TOPOLOGY'''<br /> | '''CRYSTAL STRUCTURE OF P14TCL1, AN ONCOGENE PRODUCT INVOLVED IN T-CELL PROLYMPHOCYTIC LEUKEMIA, REVEALS A NOVEL B-BARREL TOPOLOGY'''<br /> | ||
==Overview== | ==Overview== | ||
| - | BACKGROUND: Chromosome rearrangements are frequently involved in the | + | BACKGROUND: Chromosome rearrangements are frequently involved in the generation of hematopoietic tumors. One type of T-cell leukemia, T-cell prolymphocytic leukemia, is consistently associated with chromosome rearrangements characterized by the juxtaposition of the TCRA locus on chromosome 14q11 and either the TCL1 gene on 14q32.1 or the MTCP1 gene on Xq28. The TCL1 gene is preferentially expressed in cells of early lymphoid lineage; its product is a 14 kDa protein (p14TCL1), expressed in the cytoplasm. p14TCL1 has strong sequence similarity with one product of the MTCP1 gene, p13MTCP1 (41% identical and 61% similar). The functions of the TCL1 and MTCP1 genes are not known yet. They have no sequence similarity to any other published sequence, including those of well-documented oncogene families responsible for leukemia. In order to gain a more fundamental insight into the role of this particular class of oncogenes, we have determined the three-dimensional structure of p14TCL1. RESULTS: The crystal structure of p14TCL1 has been determined at 2.5 A resolution. The structure was solved by molecular replacement using the solution structure of p13MTCP1, revealing p14TCL1 to be an all-beta protein consisting of an eight-stranded antiparallel beta barrel with a novel topology. The barrel consists of two four-stranded beta-meander motifs, related by a twofold axis and connected by a long loop. This internal pseudo-twofold symmetry was not expected on basis of the sequence alone, but structure-based sequence analysis of the two motifs shows that they are related. The structures of p13MTCP1 and p14TCL1 are very similar, diverging only in regions that are either flexible and/or involved in crystal packing. p14TCL1 forms a tight crystallographic dimer, probably corresponding to the 28 kDa species identified in solution by gel filtration experiments. CONCLUSIONS: Structural similarities between p14TCL1 and p13MTCP1 suggest that their (unknown) function may be analogous. This is confirmed by the fact that these proteins are implicated in analogous diseases. Their structure does not show similarity to other oncoproteins of known structure, confirming their classification as a novel class of oncoproteins. |
==Disease== | ==Disease== | ||
| Line 11: | Line 10: | ||
==About this Structure== | ==About this Structure== | ||
| - | 1JSG is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1JSG is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JSG OCA]. |
==Reference== | ==Reference== | ||
| Line 19: | Line 18: | ||
[[Category: Guignard, L.]] | [[Category: Guignard, L.]] | ||
[[Category: Hoh, F.]] | [[Category: Hoh, F.]] | ||
| - | [[Category: Lhoste, J | + | [[Category: Lhoste, J M.]] |
[[Category: Padilla, A.]] | [[Category: Padilla, A.]] | ||
| - | [[Category: Stern, R | + | [[Category: Stern, R H.]] |
| - | [[Category: Tilbeurgh, H | + | [[Category: Tilbeurgh, H Van.]] |
| - | [[Category: Yang, Y | + | [[Category: Yang, Y S.]] |
[[Category: cl1 gene]] | [[Category: cl1 gene]] | ||
[[Category: microsome]] | [[Category: microsome]] | ||
| Line 30: | Line 29: | ||
[[Category: t cell leukemia]] | [[Category: t cell leukemia]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:26:14 2008'' |
Revision as of 11:26, 21 February 2008
|
CRYSTAL STRUCTURE OF P14TCL1, AN ONCOGENE PRODUCT INVOLVED IN T-CELL PROLYMPHOCYTIC LEUKEMIA, REVEALS A NOVEL B-BARREL TOPOLOGY
Contents |
Overview
BACKGROUND: Chromosome rearrangements are frequently involved in the generation of hematopoietic tumors. One type of T-cell leukemia, T-cell prolymphocytic leukemia, is consistently associated with chromosome rearrangements characterized by the juxtaposition of the TCRA locus on chromosome 14q11 and either the TCL1 gene on 14q32.1 or the MTCP1 gene on Xq28. The TCL1 gene is preferentially expressed in cells of early lymphoid lineage; its product is a 14 kDa protein (p14TCL1), expressed in the cytoplasm. p14TCL1 has strong sequence similarity with one product of the MTCP1 gene, p13MTCP1 (41% identical and 61% similar). The functions of the TCL1 and MTCP1 genes are not known yet. They have no sequence similarity to any other published sequence, including those of well-documented oncogene families responsible for leukemia. In order to gain a more fundamental insight into the role of this particular class of oncogenes, we have determined the three-dimensional structure of p14TCL1. RESULTS: The crystal structure of p14TCL1 has been determined at 2.5 A resolution. The structure was solved by molecular replacement using the solution structure of p13MTCP1, revealing p14TCL1 to be an all-beta protein consisting of an eight-stranded antiparallel beta barrel with a novel topology. The barrel consists of two four-stranded beta-meander motifs, related by a twofold axis and connected by a long loop. This internal pseudo-twofold symmetry was not expected on basis of the sequence alone, but structure-based sequence analysis of the two motifs shows that they are related. The structures of p13MTCP1 and p14TCL1 are very similar, diverging only in regions that are either flexible and/or involved in crystal packing. p14TCL1 forms a tight crystallographic dimer, probably corresponding to the 28 kDa species identified in solution by gel filtration experiments. CONCLUSIONS: Structural similarities between p14TCL1 and p13MTCP1 suggest that their (unknown) function may be analogous. This is confirmed by the fact that these proteins are implicated in analogous diseases. Their structure does not show similarity to other oncoproteins of known structure, confirming their classification as a novel class of oncoproteins.
Disease
Known diseases associated with this structure: Leukemia/lymphoma, T-cell OMIM:[186960]
About this Structure
1JSG is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structure of p14TCL1, an oncogene product involved in T-cell prolymphocytic leukemia, reveals a novel beta-barrel topology., Hoh F, Yang YS, Guignard L, Padilla A, Stern MH, Lhoste JM, van Tilbeurgh H, Structure. 1998 Feb 15;6(2):147-55. PMID:9519406
Page seeded by OCA on Thu Feb 21 13:26:14 2008
