PMID- 10080895
OWN - NLM
STAT- MEDLINE
DCOM- 19990428
LR  - 20190710
IS  - 0022-2836 (Print)
IS  - 0022-2836 (Linking)
VI  - 287
IP  - 2
DP  - 1999 Mar 26
TI  - Structure, backbone dynamics and interactions with RNA of the C-terminal
      RNA-binding domain of a mouse neural RNA-binding protein, Musashi1.
PG  - 315-30
AB  - Musashi1 is an RNA-binding protein abundantly expressed in the developing mouse
      central nervous system. Its restricted expression in neural precursor cells
      suggests that it is involved in the regulation of asymmetric cell division.
      Musashi1 contains two ribonucleoprotein (RNP)-type RNA-binding domains (RBDs),
      RBD1 and RBD2. Our previous studies showed that RBD1 alone binds to RNA, while
      the binding of RBD2 is not detected under the same conditions. Joining of RBD2 to
      RBD1, however, increases the affinity to greater than that of RBD1 alone,
      indicating that RBD2 contributes to RNA-binding. We have determined the
      three-dimensional solution structure of the C-terminal RBD (RBD2) of Musashi1 by 
      NMR. It folds into a compact alpha beta structure comprising a four-stranded
      antiparallel beta-sheet packed against two alpha-helices, which is characteristic
      of RNP-type RBDs. Special structural features of RBD2 include a beta-bulge in
      beta2 and a shallow twist of the beta-sheet. The smaller 1H-15N nuclear
      Overhauser enhancement values for the residues of loop 3 between beta2 and beta3 
      suggest that this loop is flexible in the time-scale of nano- to picosecond
      order. The smaller 15N T2 values for the residues around the border between
      alpha2 and the following loop (loop 5) suggest this region undergoes
      conformational exchange in the milli- to microsecond time-scale. Chemical shift
      perturbation analysis indicated that RBD2 binds to an RNA oligomer obtained by in
      vitro selection under the conditions for NMR measurements, and thus the nature of
      the weak RNA-binding of RBD2 was successfully characterized by NMR, which is
      otherwise difficult to assess. Mainly the residues of the surface composed of the
      four-stranded beta-sheet, loops and C-terminal region are involved in the
      interaction. The appearance of side-chain NH proton resonances of arginine
      residues of loop 3 and imino proton resonances of RNA bases upon complex
      formation suggests the formation of intermolecular hydrogen bonds. The structural
      arrangement of the rings of the conserved aromatic residues of beta2 and beta3 is
      suitable for stacking interaction with RNA bases, known to be one of the major
      protein-RNA interactions, but a survey of the perturbation data suggested that
      the stacking interaction is not ideally achieved in the complex, which may be
      related to the weaker RNA-binding of RBD2.
CI  - Copyright 1999 Academic Press.
FAU - Nagata, T
AU  - Nagata T
AD  - Department of Chemistry and Biotechnology, Faculty of Engineering, Yokohama
      National University, 79-5 Tokiwadai, Hodogaya-ku, Yokohama, 240-8501, Japan.
FAU - Kanno, R
AU  - Kanno R
FAU - Kurihara, Y
AU  - Kurihara Y
FAU - Uesugi, S
AU  - Uesugi S
FAU - Imai, T
AU  - Imai T
FAU - Sakakibara, S
AU  - Sakakibara S
FAU - Okano, H
AU  - Okano H
FAU - Katahira, M
AU  - Katahira M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Mol Biol
JT  - Journal of molecular biology
JID - 2985088R
RN  - 0 (Msi1h protein, mouse)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Oligoribonucleotides)
RN  - 0 (RNA-Binding Proteins)
RN  - 63231-63-0 (RNA)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Hydrogen Bonding
MH  - Magnetic Resonance Spectroscopy
MH  - Mice
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Nerve Tissue Proteins/*chemistry/metabolism
MH  - Oligoribonucleotides/chemistry
MH  - Protein Structure, Secondary
MH  - RNA/*metabolism
MH  - RNA-Binding Proteins/*chemistry/metabolism
EDAT- 1999/03/19 00:00
MHDA- 1999/03/19 00:01
CRDT- 1999/03/19 00:00
PHST- 1999/03/19 00:00 [pubmed]
PHST- 1999/03/19 00:01 [medline]
PHST- 1999/03/19 00:00 [entrez]
AID - S0022283699925962 [pii]
AID - 10.1006/jmbi.1999.2596 [doi]
PST - ppublish
SO  - J Mol Biol. 1999 Mar 26;287(2):315-30. doi: 10.1006/jmbi.1999.2596.