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PDBsum entry 1khm

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protein links
RNA binding protein PDB id
1khm
Jmol
Contents
Protein chain
89 a.a. *
* Residue conservation analysis
PDB id:
1khm
Name: RNA binding protein
Title: C-terminal kh domain of hnrnp k (kh3)
Structure: Protein (hnrnp k). Chain: a. Fragment: c-terminal kh domain, residues 379-463 of full length hnrnp k. Synonym: kh3. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
NMR struc: 20 models
Authors: J.Baber,D.Libutti,D.Levens,N.Tjandra
Key ref:
J.L.Baber et al. (1999). High precision solution structure of the C-terminal KH domain of heterogeneous nuclear ribonucleoprotein K, a c-myc transcription factor. J Mol Biol, 289, 949-962. PubMed id: 10369774 DOI: 10.1006/jmbi.1999.2818
Date:
07-Jan-99     Release date:   12-Jan-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P61978  (HNRPK_HUMAN) -  Heterogeneous nuclear ribonucleoprotein K
Seq:
Struc:
463 a.a.
89 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 4 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biochemical function     nucleic acid binding     2 terms  

 

 
DOI no: 10.1006/jmbi.1999.2818 J Mol Biol 289:949-962 (1999)
PubMed id: 10369774  
 
 
High precision solution structure of the C-terminal KH domain of heterogeneous nuclear ribonucleoprotein K, a c-myc transcription factor.
J.L.Baber, D.Libutti, D.Levens, N.Tjandra.
 
  ABSTRACT  
 
Among it's many reported functions, heterogeneous nuclear ribonucleoprotein (hnRNP) K is a transcription factor for the c- myc gene, a proto-oncogene critical for the regulation of cell growth and differentiation. We have determined the solution structure of the Gly26-->Arg mutant of the C-terminal K-homology (KH) domain of hnRNP K by NMR spectroscopy. This is the first structure investigation of hnRNP K. Backbone residual dipolar couplings, which provide information that is fundamentally different from the standard NOE-derived distance restraints, were employed to improve structure quality. An independent assessment of structure quality was achieved by comparing the backbone15N T1/T2ratios to the calculated structures. The C-terminal KH module of hnRNP K (KH3) is revealed to be a three-stranded beta-sheet stacked against three alpha-helices, two of which are nearly parallel to the strands of the beta-sheet. The Gly26-->Arg mutation abolishes single-stranded DNA binding without altering the overall fold of the protein. This provides a clue to possible nucleotide binding sites of KH3. It appears unlikely that the solvent-exposed side of the beta-sheet will be the site of protein-nucleic acid complex formation. This is in contrast to the earlier theme for protein-RNA complexes incorporating proteins structurally similar to KH3. We propose that the surface of KH3 that interacts with nucleic acid is comparable to the region of DNA interaction for the double-stranded DNA-binding domain of bovine papillomavirus-1 E2 that has a three-dimensional fold similar to that of KH3.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Histograms of the dipo- lar couplings. It is apparent that the individual distributions shown in the histograms for N-H (a), C a - H a (b), C0-N (c), and C a -C0 (d) do not reflect a powder pattern distri- bution as a result of the high con- tent of regular secondary structure. The collective distribution obtained by normalizing the C a -H a , C0-N, and C a -C0 dipolar couplings to those of N-H by the appropriate factor containing their bond length and gyromagnetic ratio (i.e. gNgH hr NH-3 i/g AgB hr AB-3 i where rAB is the bond distance between A and B and gi is the gyromagnetic ratio of i, provides a better representation of a powder pattern distribution shown in (e). The factors used for each set of dipolar couplings were 0.46, 8.3, and 5.0 for C a -H a , C0-N, and C a -C0, respectively.
Figure 8.
Figure 8. MOLMOL (Koradi et al., 1996) surface representations of (a) KH3 (residues 12-84; lowest energy of 100 calculated structures) and (b) bovine papillomavirus-1 E2 (resi- dues 326-406 shown). Positively charged areas are colored blue and negatively charged areas are in red. These representations were gener- ated by first least squares fitting E2 to KH3 and then rotating the bun- dle to best display the dsDNA- binding region of E2 (i.e. the rela- tive orientation between the two surfaces is determined by a least squares fit of the protein back- bones). (c) The ribbon diagram of KH3 with basic residue side-chain heavy atoms and bonds displayed. R26, the mutated residue, is shown in yellow. The orientation of this diagram is equivalent to that of the structure used to generate (a).
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (1999, 289, 949-962) copyright 1999.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20499280 F.Wen, A.Shen, R.Shanas, A.Bhattacharyya, F.Lian, G.Hostetter, and J.Shi (2010).
Higher expression of the heterogeneous nuclear ribonucleoprotein k in melanoma.
  Ann Surg Oncol, 17, 2619-2627.  
19609950 R.Zhou, R.Shanas, M.A.Nelson, A.Bhattacharyya, and J.Shi (2010).
Increased expression of the heterogeneous nuclear ribonucleoprotein K in pancreatic cancer and its association with the mutant p53.
  Int J Cancer, 126, 395-404.  
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.  
17437720 M.F.García-Mayoral, D.Hollingworth, L.Masino, I.Díaz-Moreno, G.Kelly, R.Gherzi, C.F.Chou, C.Y.Chen, and A.Ramos (2007).
The structure of the C-terminal KH domains of KSRP reveals a noncanonical motif important for mRNA degradation.
  Structure, 15, 485-498.
PDB codes: 2hh2 2hh3
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
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.  
15731341 M.Sidiqi, J.A.Wilce, J.P.Vivian, C.J.Porter, A.Barker, P.J.Leedman, and M.C.Wilce (2005).
Structure and RNA binding of the third KH domain of poly(C)-binding protein 1.
  Nucleic Acids Res, 33, 1213-1221.
PDB code: 1wvn
14973140 J.N.Lindquist, C.J.Parsons, B.Stefanovic, and D.A.Brenner (2004).
Regulation of alpha1(I) collagen messenger RNA decay by interactions with alphaCP at the 3'-untranslated region.
  J Biol Chem, 279, 23822-23829.  
14744980 Y.Qu, J.T.Guo, V.Olman, and Y.Xu (2004).
Protein structure prediction using sparse dipolar coupling data.
  Nucleic Acids Res, 32, 551-561.  
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.  
12592003 A.Ramos, D.Hollingworth, and A.Pastore (2003).
The role of a clinically important mutation in the fold and RNA-binding properties of KH motifs.
  RNA, 9, 293-298.  
14668443 J.Meiler, and D.Baker (2003).
Rapid protein fold determination using unassigned NMR data.
  Proc Natl Acad Sci U S A, 100, 15404-15409.  
14643926 K.E.Lukong, and S.Richard (2003).
Sam68, the KH domain-containing superSTAR.
  Biochim Biophys Acta, 1653, 73-86.  
11914064 A.Ramos, D.Hollingworth, S.A.Major, S.Adinolfi, G.Kelly, F.W.Muskett, and A.Pastore (2002).
Role of dimerization in KH/RNA complexes: the example of Nova KH3.
  Biochemistry, 41, 4193-4201.  
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.  
12093748 D.T.Braddock, J.L.Baber, D.Levens, and G.M.Clore (2002).
Molecular basis of sequence-specific single-stranded DNA recognition by KH domains: solution structure of a complex between hnRNP K KH3 and single-stranded DNA.
  EMBO J, 21, 3476-3485.
PDB code: 1j5k
11753425 J.P.Staley (2002).
Hanging on to the branch.
  Nat Struct Biol, 9, 5-7.  
11739741 O.Denisenko, and K.Bomsztyk (2002).
Yeast hnRNP K-like genes are involved in regulation of the telomeric position effect and telomere length.
  Mol Cell Biol, 22, 286-297.  
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.  
11160884 N.V.Grishin (2001).
KH domain: one motif, two folds.
  Nucleic Acids Res, 29, 638-643.  
11352723 S.Raveh, J.Vinh, J.Rossier, F.Agou, and M.Véron (2001).
Peptidic determinants and structural model of human NDP kinase B (Nm23-H2) bound to single-stranded DNA.
  Biochemistry, 40, 5882-5893.  
10676814 H.A.Lewis, K.Musunuru, K.B.Jensen, C.Edo, H.Chen, R.B.Darnell, and S.K.Burley (2000).
Sequence-specific RNA binding by a Nova KH domain: implications for paraneoplastic disease and the fragile X syndrome.
  Cell, 100, 323-332.
PDB code: 1ec6
10821674 J.L.Baber, D.Levens, D.Libutti, and N.Tjandra (2000).
Chemical shift mapped DNA-binding sites and 15N relaxation analysis of the C-terminal KH domain of heterogeneous nuclear ribonucleoprotein K.
  Biochemistry, 39, 6022-6032.  
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.  
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 codes are shown on the right.

 

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