PDBsum entry: 1dtj

Immune system

PDB-id

1dtj

	Biological unit* = asymmetric unit, as shown (as deduced by PQS*)


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Description

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Protein chains

Waters ×211

* Residue conservation analysis

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PDB id:

1dtj

Name:

Immune system

Title:

Crystal structure of nova-2 kh3 k-homology RNA-binding domain

Structure:

RNA-binding neurooncological ventral antigen 2. Chain: a, b, c, d. Fragment: third kh domain of nova-2. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Organ: brain. Cell: neuron. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biological unit:

Tetramer (from PQS)

UniProt:

Chain A: Q9UNW9 (NOVA2_HUMAN)

Seq:

Struc:


Seq:				492 a.a.

Struc:				74 a.a.*

Chain B: Q9UNW9 (NOVA2_HUMAN)

Seq:

Struc:


Seq:				492 a.a.

Struc:				62 a.a.*

Chain C: Q9UNW9 (NOVA2_HUMAN)

Seq:

Struc:


Seq:				492 a.a.

Struc:				66 a.a.*

Chain D: Q9UNW9 (NOVA2_HUMAN)

Seq:

Struc:

Seq:

492 a.a.

Struc:

64 a.a.*

Key:		PfamA domain
		Secondary structure			CATH domain

* PDB and UniProt seqs differ at 8 residue positions (black crosses)

Resolution:

2.00Å

R-factor:

0.225

R-free:

0.279

Authors:

H.A.Lewis,H.Chen,C.Edo,R.J.Buckanovich,Y.Y.L.Yang, K.Musunuru,R.Zhong,R.B.Darnell,S.K.Burley

Key ref:

H.A.Lewis et al. (1999). Crystal structures of Nova-1 and Nova-2 K-homology RNA-binding domains.. Structure, 7, 191-203. [PubMed id: 10368286] [DOI: 10.1016/S0969-2126(99)80025-2]

Date:

12-Jan-00

Release date:

18-Feb-00

Related entries:

1dt4
crystal structure of nova-1 kh3 k-homology RNA-binding
domain
1ec6
same protein with RNA

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Key reference

DOI no: 10.1016/S0969-2126(99)80025-2 Structure 7:191-203 (1999)

PubMed id: 10368286

Crystal structures of Nova-1 and Nova-2 K-homology RNA-binding domains.

H.A.Lewis, H.Chen, C.Edo, R.J.Buckanovich, Y.Y.Yang, K.Musunuru, R.Zhong, R.B.Darnell, S.K.Burley.

ABSTRACT

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.

Selected figure(s)

Figure 3.
Figure 3. Structure of a Nova KH domain. Ribbon stereodrawing of Nova-2 KH3 with conserved aliphatic residues comprising the hydrophobic core illustrated in ball-and-stick format. The invariant Gly–X–X–Gly segment is shown in yellow, and the variable loop in red. The N and C termini are indicated. (a) A view of the β-sheet face of the KH domain. (b) A 90° rotation from the view shown in (a).

The above figure is reprinted by permission from Cell Press: Structure (1999, 7, 191-203) copyright 1999.

Figure was selected by an automated process.

Literature references that cite this PDB file's key reference

PubMed id Reference

19487368 J.C.Darnell, C.E.Fraser, O.Mostovetsky, and R.B.Darnell (2009).
Discrimination of common and unique RNA-binding activities among Fragile X mental retardation protein paralogs.

Hum Mol Genet, 18, 3164-3177.

19143590 L.Sjekloća, P.V.Konarev, J.Eccleston, I.A.Taylor, D.I.Svergun, and A.Pastore (2009).
A study of the ultrastructure of fragile-X-related proteins.

Biochem J, 419, 347-357.

18422648 R.Valverde, L.Edwards, and L.Regan (2008).
Structure and function of KH domains.

FEBS J, 275, 2712-2726.

18701464 Z.Du, S.Fenn, R.Tjhen, and T.L.James (2008).
Structure of a Construct of a Human Poly(C)-binding Protein Containing the First and Second KH Domains Reveals Insights into Its Regulatory Mechanisms.

J Biol Chem, 283, 28757-28766.

17264125 M.A.Brykailo, A.H.Corbett, and J.L.Fridovich-Keil (2007).
Functional overlap between conserved and diverged KH domains in Saccharomyces cerevisiae SCP160.

Nucleic Acids Res, 35, 1108-1118.

17426136 S.Fenn, Z.Du, J.K.Lee, R.Tjhen, R.M.Stroud, and T.L.James (2007).
Crystal structure of the third KH domain of human poly(C)-binding protein-2 in complex with a C-rich strand of human telomeric DNA at 1.6 A resolution.

Nucleic Acids Res, 35, 2651-2660.

PDB code: 2p2r

16428607 N.H.Chmiel, D.C.Rio, and J.A.Doudna (2006).
Distinct contributions of KH domains to substrate binding affinity of Drosophila P-element somatic inhibitor protein.

RNA, 12, 283-291.

17381312 R.B.Darnell (2006).
Developing global insight into RNA regulation.

Cold Spring Harb Symp Quant Biol, 71, 321-327.

16476777 T.P.Munro, S.Kwon, B.J.Schnapp, and D.St Johnston (2006).
A repeated IMP-binding motif controls oskar mRNA translation and anchoring independently of Drosophila melanogaster IMP.

J Cell Biol, 172, 577-588.

15670167 I.Pozdnyakova, and L.Regan (2005).
New insights into Fragile X syndrome. Relating genotype to phenotype at the molecular level.

FEBS J, 272, 872-878.

15805463 J.C.Darnell, C.E.Fraser, O.Mostovetsky, G.Stefani, T.A.Jones, S.R.Eddy, and R.B.Darnell (2005).
Kissing complex RNAs mediate interaction between the Fragile-X mental retardation protein KH2 domain and brain polyribosomes.

Genes Dev, 19, 903-918.

16098133 J.C.Darnell, O.Mostovetsky, and R.B.Darnell (2005).
FMRP RNA targets: identification and validation.

Genes Brain Behav, 4, 341-349.

15756586 M.Sidiqi, J.A.Wilce, C.J.Porter, A.Barker, P.J.Leedman, and M.C.Wilce (2005).
Formation of an alphaCP1-KH3 complex with UC-rich RNA.

Eur Biophys J, 34, 423-429.

16041073 R.Caliandro, B.Carrozzini, G.L.Cascarano, L.De Caro, C.Giacovazzo, and D.Siliqi (2005).
Ab initio phasing at resolution higher than experimental resolution.

Acta Crystallogr D Biol Crystallogr, 61, 1080-1087.

16186123 Z.Du, J.K.Lee, R.Tjhen, S.Li, H.Pan, R.M.Stroud, and T.L.James (2005).
Crystal structure of the first KH domain of human poly(C)-binding protein-2 in complex with a C-rich strand of human telomeric DNA at 1.7 A.

J Biol Chem, 280, 38823-38830.

PDB code: 2axy

15367696 K.Musunuru, and R.B.Darnell (2004).
Determination and augmentation of RNA sequence specificity of the Nova K-homology domains.

Nucleic Acids Res, 32, 4852-4861.

15331611 Z.Du, J.Yu, Y.Chen, R.Andino, and T.L.James (2004).
Specific recognition of the C-rich strand of human telomeric DNA and the RNA template of human telomerase by the first KH domain of human poly(C)-binding protein-2.

J Biol Chem, 279, 48126-48134.

14612387 A.N.Chkheidze, and S.A.Liebhaber (2003).
A novel set of nuclear localization signals determine distributions of the alphaCP RNA-binding proteins.

Mol Cell Biol, 23, 8405-8415.

12808107 B.K.Dredge, and R.B.Darnell (2003).
Nova regulates GABA(A) receptor gamma2 alternative splicing via a distal downstream UCAU-rich intronic splicing enhancer.

Mol Cell Biol, 23, 4687-4700.

12972621 S.A.Waggoner, and S.A.Liebhaber (2003).
Identification of mRNAs associated with alphaCP2-containing RNP complexes.

Mol Cell Biol, 23, 7055-7067.

12403469 A.Git, and N.Standart (2002).
The KH domains of Xenopus Vg1RBP mediate RNA binding and self-association.

RNA, 8, 1319-1333.

12003487 A.V.Makeyev, and S.A.Liebhaber (2002).
The poly(C)-binding proteins: a multiplicity of functions and a search for mechanisms.

RNA, 8, 265-278.

12414943 B.L.Walter, T.B.Parsley, E.Ehrenfeld, and B.L.Semler (2002).
Distinct poly(rC) binding protein KH domain determinants for poliovirus translation initiation and viral RNA replication.

J Virol, 76, 12008-12022.

11753425 J.P.Staley (2002).
Hanging on to the branch.

Nat Struct Biol, 9, 5-7.

11481485 A.Beletskii, Y.K.Hong, J.Pehrson, M.Egholm, and W.M.Strauss (2001).
PNA interference mapping demonstrates functional domains in the noncoding RNA Xist.

Proc Natl Acad Sci U S A, 98, 9215-9220.

11565747 A.K.Amarasinghe, R.MacDiarmid, M.D.Adams, and D.C.Rio (2001).
An in vitro-selected RNA-binding site for the KH domain protein PSI acts as a splicing inhibitor element.

RNA, 7, 1239-1253.

11438677 H.Peled-Zehavi, J.A.Berglund, M.Rosbash, and A.D.Frankel (2001).
Recognition of RNA branch point sequences by the KH domain of splicing factor 1 (mammalian branch point binding protein) in a splicing factor complex.

Mol Cell Biol, 21, 5232-5241.

11283311 K.Musunuru, and R.B.Darnell (2001).
Paraneoplastic neurologic disease antigens: RNA-binding proteins and signaling proteins in neuronal degeneration.

Annu Rev Neurosci, 24, 239-262.

11160884 N.V.Grishin (2001).
KH domain: one motif, two folds.

Nucleic Acids Res, 29, 638-643.

11340052 S.L.Cohen, and B.T.Chait (2001).
Mass spectrometry as a tool for protein crystallography.

Annu Rev Biophys Biomol Struct, 30, 67-85.

11733036 T.Akiyama, J.Gohda, S.Shibata, Y.Nomura, S.Azuma, Y.Ohmori, S.Sugano, H.Arai, T.Yamamoto, and J.Inoue (2001).
Mammalian homologue of E. coli Ras-like GTPase (ERA) is a possible apoptosis regulator with RNA binding activity.

Genes Cells, 6, 987.

11691992 Z.Liu, I.Luyten, M.J.Bottomley, A.C.Messias, S.Houngninou-Molango, R.Sprangers, K.Zanier, A.Krämer, and M.Sattler (2001).
Structural basis for recognition of the intron branch site RNA by splicing factor 1.

Science, 294, 1098-1102.

PDB code: 1k1g

10805729 A.Cortés, and F.Azorín (2000).
DDP1, a heterochromatin-associated multi-KH-domain protein of Drosophila melanogaster, interacts specifically with centromeric satellite DNA sequences.

Mol Cell Biol, 20, 3860-3869.

10811881 K.B.Jensen, K.Musunuru, H.A.Lewis, S.K.Burley, and R.B.Darnell (2000).
The tetranucleotide UCAY directs the specific recognition of RNA by the Nova K-homology 3 domain.

Proc Natl Acad Sci U S A, 97, 5740-5745.

10608888 D.Silvera, A.V.Gamarnik, and R.Andino (1999).
The N-terminal K homology domain of the poly(rC)-binding protein is a major determinant for binding to the poliovirus 5'-untranslated region and acts as an inhibitor of viral translation.

J Biol Chem, 274, 38163-38170.

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.