Crystal and solution structures of human oncoprotein Musashi-2 N-terminal RNA recognition motif 1.
Amino Acid Sequence
Binding Sites
Crystallography, X-Ray
Humans
Models, Molecular
Nerve Tissue Proteins
/ chemistry
Nuclear Magnetic Resonance, Biomolecular
Oncogene Proteins
/ chemistry
Protein Binding
Protein Conformation, alpha-Helical
Protein Conformation, beta-Strand
Protein Folding
Protein Interaction Domains and Motifs
RNA Recognition Motif
RNA, Messenger
/ chemistry
RNA-Binding Proteins
/ chemistry
Sequence Alignment
Sequence Homology, Amino Acid
Thermodynamics
Musashi
RNA-binding pocket
RNA-binding protein
crystallography
nuclear magnetic resonance
Journal
Proteins
ISSN: 1097-0134
Titre abrégé: Proteins
Pays: United States
ID NLM: 8700181
Informations de publication
Date de publication:
04 2020
04 2020
Historique:
received:
06
05
2019
revised:
16
09
2019
accepted:
28
09
2019
pubmed:
12
10
2019
medline:
5
1
2021
entrez:
12
10
2019
Statut:
ppublish
Résumé
Musashi-2 (MSI2) belongs to Musashi family of RNA binding proteins (RBP). 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 posttranscriptional 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 RBPs. 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 RBPs. The structural information of MSI2-RRM1 will be helpful for understanding MSI2-RNA interaction and for guiding rational drug design of MSI2-specific inhibitors.
Identifiants
pubmed: 31603583
doi: 10.1002/prot.25836
pmc: PMC7079100
mid: NIHMS1541056
doi:
Substances chimiques
MSI1 protein, human
0
MSI2 protein, human
0
Nerve Tissue Proteins
0
Oncogene Proteins
0
RNA, Messenger
0
RNA-Binding Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
573-583Subventions
Organisme : NCI NIH HHS
ID : R01 CA191785
Pays : United States
Organisme : NIGMS NIH HHS
ID : P30 GM110761
Pays : United States
Organisme : NIH HHS
ID : R01 CA178831
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA178831
Pays : United States
Organisme : NIH HHS
ID : p41 GM111135
Pays : United States
Organisme : NIH HHS
ID : R01 CA191785
Pays : United States
Organisme : NIH HHS
ID : P30 GM110761
Pays : United States
Organisme : NIGMS NIH HHS
ID : P41 GM111135
Pays : United States
Informations de copyright
© 2019 The Authors. Proteins: Structure, Function, and Bioinformatics published by Wiley Periodicals, Inc.
Références
Science. 2012 May 25;336(6084):986-7
pubmed: 22628641
J Biomol NMR. 1995 Nov;6(3):277-93
pubmed: 8520220
Nature. 2016 Jun 06;534(7607):407-411
pubmed: 27281208
Oncotarget. 2017 Nov 20;8(63):106587-106597
pubmed: 29290973
Blood. 2011 Sep 8;118(10):2857-67
pubmed: 21753187
PLoS One. 2015 Aug 26;10(8):e0136484
pubmed: 26308531
Nat Commun. 2019 Jun 19;10(1):2691
pubmed: 31217428
Nucleic Acids Res. 2000 Apr 15;28(8):1743-50
pubmed: 10734193
J Biomol NMR. 2013 Jan;55(1):119-38
pubmed: 23247503
Proteins. 2005 Jun 1;59(4):687-96
pubmed: 15815974
Proteins. 2020 Apr;88(4):573-583
pubmed: 31603583
Science. 2012 May 25;336(6084):1030-3
pubmed: 22628654
Ann Hematol. 2013 Mar;92(3):315-23
pubmed: 23233047
Cancer Biol Ther. 2010 Nov 15;10(10):979-82
pubmed: 21084860
J Biomol NMR. 1994 Sep;4(5):603-14
pubmed: 22911360
Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2288-94
pubmed: 15572783
Mol Oncol. 2015 Aug;9(7):1406-20
pubmed: 25933687
Acta Crystallogr D Biol Crystallogr. 2011 Apr;67(Pt 4):282-92
pubmed: 21460446
Acta Crystallogr D Biol Crystallogr. 2006 Jan;62(Pt 1):72-82
pubmed: 16369096
Cancer Med. 2016 Apr;5(4):623-30
pubmed: 26775684
Clin Cancer Res. 2017 May 1;23(9):2143-2153
pubmed: 28143872
Acta Crystallogr D Biol Crystallogr. 2010 Jan;66(Pt 1):12-21
pubmed: 20057044
Nucleic Acids Res. 2012 Apr;40(7):3218-31
pubmed: 22140116
Acta Crystallogr D Biol Crystallogr. 1998 Sep 1;54(Pt 5):905-21
pubmed: 9757107
Annu Rev Cell Dev Biol. 2015;31:249-67
pubmed: 26566113
J Mol Biol. 1997 Sep 12;272(1):82-94
pubmed: 9299339
Mol Cell Biol. 1986 Aug;6(8):2932-43
pubmed: 3537727
Mol Cell Biol. 1987 May;7(5):1731-9
pubmed: 3110598
Trends Biochem Sci. 1988 Mar;13(3):86-91
pubmed: 3072706
Elife. 2014 Nov 07;3:e03915
pubmed: 25380226
Trends Cancer. 2017 May;3(5):347-356
pubmed: 28718412
Clin Cancer Res. 2017 Feb 1;23(3):687-696
pubmed: 27449499
Nature. 2010 Aug 5;466(7307):765-8
pubmed: 20639863
Int J Lab Hematol. 2015 Apr;37(2):272-8
pubmed: 25090928
Structure. 1997 Apr 15;5(4):559-70
pubmed: 9115444
Oncogene. 2017 Mar 23;36(12):1745-1752
pubmed: 27593929
Biochemistry. 2010 Aug 10;49(31):6576-86
pubmed: 20677832
PLoS One. 2013 May 07;8(5):e62857
pubmed: 23667531
Nat Med. 2010 Aug;16(8):903-8
pubmed: 20616797
Acta Crystallogr F Struct Biol Commun. 2017 Apr 1;73(Pt 4):209-214
pubmed: 28368279
Leuk Lymphoma. 2015 Jul;56(7):2105-13
pubmed: 25363400
Nat Commun. 2015 Mar 16;6:6517
pubmed: 25774828
Int J Oncol. 2016 Nov;49(5):1945-1952
pubmed: 27600258
Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501
pubmed: 20383002
J Mol Biochem. 2012;1(2):76-85
pubmed: 27882309
Nucleic Acids Res. 2017 Jul 3;45(W1):W550-W553
pubmed: 28431173
Acta Crystallogr D Struct Biol. 2017 Feb 1;73(Pt 2):148-157
pubmed: 28177311
Elife. 2017 Jun 26;6:
pubmed: 28650318
Nat Struct Biol. 1997 Apr;4(4):269-75
pubmed: 9095194
Proc Natl Acad Sci U S A. 2016 Jun 21;113(25):6955-60
pubmed: 27274057
Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):213-21
pubmed: 20124702
J Neurosci. 2001 Oct 15;21(20):8091-107
pubmed: 11588182
Biophys J. 2017 Apr 25;112(8):1529-1534
pubmed: 28445744
Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):125-32
pubmed: 20124692
J Biol Chem. 2014 Dec 19;289(51):35530-41
pubmed: 25368328
Nucleic Acids Res. 1997 Sep 1;25(17):3389-402
pubmed: 9254694
J Appl Crystallogr. 2007 Aug 1;40(Pt 4):658-674
pubmed: 19461840
J Mol Biol. 1968 Apr 28;33(2):491-7
pubmed: 5700707
Cell Rep. 2015 Dec 22;13(11):2440-2455
pubmed: 26673327
FASEB J. 2017 Jun;31(6):2429-2438
pubmed: 28223335