1sxe | pdb_00001sxe
The solution structure of the Pointed (PNT) domain from the transcrition factor Erg
Structural highlights
Disease[ERG_HUMAN] Defects in ERG are a cause of Ewing sarcoma (ES) [MIM:612219]. A highly malignant, metastatic, primitive small round cell tumor of bone and soft tissue that affects children and adolescents. It belongs to the Ewing sarcoma family of tumors, a group of morphologically heterogeneous neoplasms that share the same cytogenetic features. They are considered neural tumors derived from cells of the neural crest. Ewing sarcoma represents the less differentiated form of the tumors. Note=A chromosomal aberration involving ERG is found in patients with Erwing sarcoma. Translocation t(21;22)(q22;q12) with EWSR1. Note=Chromosomal aberrations involving ERG have been found in acute myeloid leukemia (AML). Translocation t(16;21)(p11;q22) with FUS. Translocation t(X;21)(q25-26;q22) with ELF4. Function[ERG_HUMAN] Transcriptional regulator. May participate in transcriptional regulation through the recruitment of SETDB1 histone methyltransferase and subsequent modification of local chromatin structure. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe PNT (or Pointed) domain, present within a subset of the Ets family of transcription factors, is structurally related to the larger group of SAM domains through a common tertiary arrangement of four alpha-helices. Previous studies have shown that, in contrast to the PNT domain from Tel, this domain from Ets-1 contains an additional N-terminal helix integral to its folded structure. To further investigate the structural plasticity of the PNT domain, we have used NMR spectroscopy to characterize this domain from two additional Ets proteins, Erg and GABPalpha. These studies both define the conserved and variable features of the PNT domain, and demonstrate that the additional N-terminal helix is also present in GABPalpha, but not Erg. In contrast to Tel and Yan, which self-associate to form insoluble polymers, we also show that the isolated PNT domains from Ets-1, Ets-2, Erg, Fli-1, GABPalpha, and Pnt-P2 are monomeric in solution. Furthermore, these soluble PNT domains do not associate in any pair-wise combination. Thus these latter Ets family PNT domains likely mediate interactions with additional components of the cellular signaling or transcriptional machinery. Diversity in structure and function of the Ets family PNT domains.,Mackereth CD, Scharpf M, Gentile LN, MacIntosh SE, Slupsky CM, McIntosh LP J Mol Biol. 2004 Sep 24;342(4):1249-64. PMID:15351649[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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