8j2q
Crystal structure of Cypovirus Polyhedra mutant fused with c-Myc fragment
Structural highlights
DiseaseMYC_HUMAN Note=Overexpression of MYC is implicated in the etiology of a variety of hematopoietic tumors. Note=A chromosomal aberration involving MYC may be a cause of a form of B-cell chronic lymphocytic leukemia. Translocation t(8;12)(q24;q22) with BTG1. Defects in MYC are a cause of Burkitt lymphoma (BL) [MIM:113970. A form of undifferentiated malignant lymphoma commonly manifested as a large osteolytic lesion in the jaw or as an abdominal mass. Note=Chromosomal aberrations involving MYC are usually found in Burkitt lymphoma. Translocations t(8;14), t(8;22) or t(2;8) which juxtapose MYC to one of the heavy or light chain immunoglobulin gene loci. FunctionPYHD_CPVBM Major component of the virus occlusion bodies, which are large proteinaceous structures (polyhedra), that protect the virus from the outside environment for extended periods until they are ingested by insect larvae.MYC_HUMAN Participates in the regulation of gene transcription. Binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. Seems to activate the transcription of growth-related genes. Publication Abstract from PubMedIntrinsically disordered proteins (IDPs) play a crucial role in various biological phenomena, dynamically changing their conformations in response to external environmental cues. To gain a deeper understanding of these proteins, it is essential to identify the determinants that fix their structures at the atomic level. Here, we developed a pipeline for rapid crystal structure analysis of IDP using a cell-free protein crystallization (CFPC) method. Through this approach, we successfully demonstrated the determination of the structure of an IDP to uncover the key determinants that stabilize its conformation. Specifically, we focused on the 11-residue fragment of c-Myc, which forms an alpha-helix through dimerization with a binding partner protein. This fragment was strategically recombined with an in-cell crystallizing protein and was expressed in a cell-free system. The resulting crystal structures of the c-Myc fragment were successfully determined at a resolution of 1.92 A and we confirmed that they are identical to the structures of the complex with the native binding partner protein. This indicates that the environment of the scaffold crystal can fix the structure of c-Myc. Significantly, these crystals were obtained directly from a small reaction mixture (30 microL) incubated for only 72 h. Analysis of eight crystal structures derived from 22 mutants revealed two hydrophobic residues as the key determinants responsible for stabilizing the alpha-helical structure. These findings underscore the power of our CFPC screening method as a valuable tool for determining the structures of challenging target proteins and elucidating the essential molecular interactions that govern their stability. High-throughput structure determination of an intrinsically disordered protein using cell-free protein crystallization.,Kojima M, Abe S, Furuta T, Hirata K, Yao X, Kobayashi A, Kobayashi R, Ueno T Proc Natl Acad Sci U S A. 2024 Jun 18;121(25):e2322452121. doi: , 10.1073/pnas.2322452121. Epub 2024 Jun 11. PMID:38861600[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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