PDBsum entry: 1khm

RNA binding protein

PDB id: 1khm

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

Protein chain

P61978  (HNRPK_HUMAN) -  Heterogeneous nuclear ribonucleoprotein K

Seq: 463 a.a.

Struc: 89 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 

• Biochemical function: RNA binding (1 term)

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.