Structural highlights
Disease
[MSI2H_HUMAN] Chromosomal aberrations involving MSI2 may contribute to disease progression in chronic myeloid leukemia. Translocation t(7;17)(p15;q23) with HOXA9; translocation t(7;17)(q32-34;q23).[1]
Function
[MSI2H_HUMAN] RNA binding protein that regulates the expression of target mRNAs at the translation level. May play a role in the proliferation and maintenance of stem cells in the central nervous system (By similarity).
Publication Abstract from PubMed
Musashi-2 (MSI2) belongs to Musashi family of RNA binding proteins. Like Musashi-1 (MSI1), it is overexpressed in a variety of cancers and is a promising therapeutic target. Both MSI proteins contain two N-terminal RNA recognition motifs and play roles in post-transcriptional regulation of target mRNAs. Previously, we have identified several inhibitors of MSI1, all of which bind to MSI2 as well. In order to design MSI2 specific inhibitors and compare the differences of binding mode of the inhibitors, we set out to solve the structure of MSI2-RRM1, the key motif that is responsible for the binding. Here we report the crystal structure and the first NMR solution structure of MSI2-RRM1, and compare these to the structures of MSI1-RBD1 and other RNA binding proteins. A high degree of structural similarity was observed between the crystal and solution NMR structures. MSI2-RRM1 shows a highly similar overall folding topology to MSI1-RBD1 and other RNA binding proteins. The structural information of MSI2-RRM1 will be helpful for understanding MSI2-RNA interaction and for guiding rational drug design of MSI2 specific inhibitors. This article is protected by copyright. All rights reserved.
Crystal and Solution Structures of Human Oncoprotein Musashi-2 N-terminal RNA Recognition Motif 1.,Lan L, Xing M, Kashipathy MM, Douglas JT, Gao P, Battaile KP, Hanzlik RP, Lovell S, Xu L Proteins. 2019 Oct 11. doi: 10.1002/prot.25836. PMID:31603583[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Barbouti A, Hoglund M, Johansson B, Lassen C, Nilsson PG, Hagemeijer A, Mitelman F, Fioretos T. A novel gene, MSI2, encoding a putative RNA-binding protein is recurrently rearranged at disease progression of chronic myeloid leukemia and forms a fusion gene with HOXA9 as a result of the cryptic t(7;17)(p15;q23). Cancer Res. 2003 Mar 15;63(6):1202-6. PMID:12649177
- ↑ Lan L, Xing M, Kashipathy MM, Douglas JT, Gao P, Battaile KP, Hanzlik RP, Lovell S, Xu L. Crystal and Solution Structures of Human Oncoprotein Musashi-2 N-terminal RNA Recognition Motif 1. Proteins. 2019 Oct 11. doi: 10.1002/prot.25836. PMID:31603583 doi:http://dx.doi.org/10.1002/prot.25836
