4irh

Auto-inhibited ERG Ets domainAuto-inhibited ERG Ets domain

Structural highlights 4irh is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.1Å Ligands: Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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. Publication Abstract from PubMed The Ets-Related Gene (ERG) belongs to the Ets family of transcription factors and is critically important for maintenance of the hematopoietic stem cell population. A chromosomal translocation observed in the majority of human prostate cancers leads to the aberrant overexpression of ERG. We have identified regions flanking the ERG Ets domain responsible for autoinhibition of DNA binding and solved crystal structures of uninhibited, autoinhibited, and DNA-bound ERG. NMR-based measurements of backbone dynamics show that uninhibited ERG undergoes substantial dynamics on the millisecond-to-microsecond timescale but autoinhibited and DNA-bound ERG do not. We propose a mechanism whereby the allosteric basis of ERG autoinhibition is mediated predominantly by the regulation of Ets-domain dynamics with only modest structural changes. Structural and dynamic studies of the transcription factor ERG reveal DNA binding is allosterically autoinhibited.,Regan MC, Horanyi PS, Pryor EE Jr, Sarver JL, Cafiso DS, Bushweller JH Proc Natl Acad Sci U S A. 2013 Jul 29. PMID:23898196 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

spinqualitylabelsall models 4irh, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image