PMID- 10368286
OWN - NLM
STAT- MEDLINE
DCOM- 19990329
LR  - 20151013
IS  - 0969-2126 (Print)
IS  - 0969-2126 (Linking)
VI  - 7
IP  - 2
DP  - 1999 Feb 15
TI  - Crystal structures of Nova-1 and Nova-2 K-homology RNA-binding domains.
PG  - 191-203
AB  - BACKGROUND: Nova-1 and Nova-2 are related neuronal proteins that were initially
      cloned using antisera obtained from patients with the autoimmune neurological
      disease paraneoplastic opsoclonus-myoclonus ataxia (POMA). Both of these disease 
      gene products contain three RNA-binding motifs known as K-homology or KH domains,
      and their RNA ligands have been identified via binding-site selection
      experiments. The KH motif structure has been determined previously using NMR
      spectroscopy, but not using X-ray crystallography. Many proteins contain more
      than one KH domain, yet there is no published structural information regarding
      the behavior of such multimers. RESULTS: We have obtained the first X-ray
      crystallographic structures of KH-domain-containing proteins. Structures of the
      third KH domains (KH3) of Nova-1 and Nova-2 were determined by multiple
      isomorphous replacement and molecular replacement at 2.6 A and 2.0 A,
      respectively. These highly similar RNA-binding motifs form a compact
      protease-resistant domain resembling an open-faced sandwich, consisting of a
      three-stranded antiparallel beta sheet topped by three alpha helices. In both
      Nova crystals, the lattice is composed of symmetric tetramers of KH3 domains that
      are created by two dimer interfaces. CONCLUSIONS: The crystal structures of both 
      Nova KH3 domains are similar to the previously determined NMR structures. The
      most significant differences among the KH domains involve changes in the
      positioning of one or more of the alpha helices with respect to the betasheet,
      particularly in the NMR structure of the KH1 domain of the Fragile X disease
      protein FMR-1. Loop regions in the KH domains are clearly visible in the crystal 
      structure, unlike the NMR structures, revealing the conformation of the invariant
      Gly-X-X-Gly segment that is thought to participate in RNA-binding and of the
      variable region. The tetrameric arrangements of the Nova KH3 domains provide
      insights into how KH domains may interact with each other in proteins containing 
      multiple KH motifs.
FAU - Lewis, H A
AU  - Lewis HA
AD  - Laboratories of Molecular Biophysics, Howard Hughes Medical Institute, The
      Rockefeller University, 1230 York Avenue, New York, NY, 10021 USA.
FAU - Chen, H
AU  - Chen H
FAU - Edo, C
AU  - Edo C
FAU - Buckanovich, R J
AU  - Buckanovich RJ
FAU - Yang, Y Y
AU  - Yang YY
FAU - Musunuru, K
AU  - Musunuru K
FAU - Zhong, R
AU  - Zhong R
FAU - Darnell, R B
AU  - Darnell RB
FAU - Burley, S K
AU  - Burley SK
LA  - eng
SI  - GENBANK/AF064634
SI  - GENBANK/AJ000051
SI  - GENBANK/J02638
SI  - GENBANK/J03453
SI  - GENBANK/L07596
SI  - GENBANK/L25598
SI  - GENBANK/M31304
SI  - GENBANK/M88108
SI  - GENBANK/M91593
SI  - GENBANK/S65791
SI  - GENBANK/S74678
SI  - GENBANK/S75665
SI  - GENBANK/U05040
SI  - GENBANK/U10438
SI  - GENBANK/U15928
SI  - GENBANK/U20535
SI  - GENBANK/U23177
SI  - GENBANK/U24223
SI  - GENBANK/U25165
SI  - GENBANK/U31501
SI  - GENBANK/U67864
SI  - GENBANK/U72331
SI  - GENBANK/U97188
SI  - GENBANK/U98432
SI  - GENBANK/X00513
SI  - GENBANK/X65292
SI  - GENBANK/X65645
SI  - GENBANK/X75947
SI  - GENBANK/X97335
SI  - GENBANK/Z34802
SI  - etc.
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Structure
JT  - Structure (London, England : 1993)
JID - 101087697
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Nova antigen)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (Ribonucleoproteins)
RN  - 63231-63-0 (RNA)
RN  - EC 3.4.- (Endopeptidases)
SB  - IM
MH  - Amino Acid Sequence
MH  - *Antigens, Neoplasm
MH  - Binding Sites
MH  - Crystallography, X-Ray
MH  - Endopeptidases/metabolism
MH  - Fragile X Syndrome/genetics
MH  - Humans
MH  - Magnetic Resonance Spectroscopy
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Nerve Tissue Proteins/chemistry
MH  - Point Mutation
MH  - Protein Conformation
MH  - Protein Structure, Secondary
MH  - RNA/metabolism
MH  - RNA-Binding Proteins/*chemistry
MH  - Ribonucleoproteins/*chemistry
MH  - Sequence Homology, Amino Acid
EDAT- 1999/06/16 00:00
MHDA- 1999/06/16 00:01
CRDT- 1999/06/16 00:00
PHST- 1999/06/16 00:00 [pubmed]
PHST- 1999/06/16 00:01 [medline]
PHST- 1999/06/16 00:00 [entrez]
AID - S0969-2126(99)80025-2 [pii]
AID - 10.1016/S0969-2126(99)80025-2 [doi]
PST - ppublish
SO  - Structure. 1999 Feb 15;7(2):191-203. doi: 10.1016/S0969-2126(99)80025-2.