PDBsum entry 1f95

Contractile protein/peptide

PDB id: 1f95

Contents

Protein chains

89 a.a. *

Ligands

MET-SER-CYS-ASP-LYS-SER-THR-GLN-THR ×2

* Residue conservation analysis

PDB id:

1f95

Name:

Contractile protein/peptide

Title:

Solution structure of dynein light chain 8 (dlc8) and bim peptide complex

Structure:

Dynein. Chain: a, b. Fragment: 8kda light chain. Synonym: protein inhibitor of neuronal nitric oxide synthase, dlc8. Engineered: yes. Bcl2-like 11 (apoptosis facilitator). Chain: c, d. Fragment: dlc8 binding region. Engineered: yes

Source:

Rattus norvegicus. Norway rat. Organism_taxid: 10116. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: this peptide was chemically synthesized. This sequence occurs naturally in humans (homo sapiens)

NMR struc:

1 models

Authors:

J.-S.Fan,Q.Zhang,H.Tochio,M.Li,M.Zhang

Key ref:

J.Fan et al. (2001). Structural basis of diverse sequence-dependent target recognition by the 8 kDa dynein light chain. J Mol Biol, 306, 97. PubMed id: 11178896 DOI: 10.1006/jmbi.2000.4374

Date:

07-Jul-00 Release date: 28-Feb-01

Protein chains

P63170  (DYL1_RAT) -  Dynein light chain 1, cytoplasmic from Rattus norvegicus

Seq: 89 a.a.

Struc: 89 a.a.

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1006/jmbi.2000.4374

J Mol Biol 306:97 (2001)

PubMed id: 11178896

Structural basis of diverse sequence-dependent target recognition by the 8 kDa dynein light chain.

J.Fan, Q.Zhang, H.Tochio, M.Li, M.Zhang.

ABSTRACT

Dyneins are multi-subunit molecular motors that translocate molecular cargoes along microtubules. Other than acting as an essential component of the dynein motor complex, the 89-residue subunit of dynein light chain (DLC8) also regulates a number of other biological events by binding to various proteins and enzymes. Currently known DLC8 targets include neuronal nitric oxide synthase; the proapoptotic Bcl-2 family member protein designated Bim; a Drosophila RNA localization protein Swallow, myosin V, neuronal scaffolding protein GKAP, and IkappaBalpha, an inhibitor of the NFkappaB transcription factor. The DLC8-binding domains of the various targets are confined within a short, continuous stretch of amino acid residues. However, these domains do not share any obvious sequence homology with each other. Here, the three-dimensional structures of DLC8 complexed with two peptides corresponding to the DLC8-binding domains of neuronal nitric oxide synthase and Bim, respectively, were determined by NMR spectroscopy. Although the two DLC8-binding peptides have entirely different amino acid sequences, both peptides bind to the protein with a remarkable similar conformation by engaging the symmetric DLC8 dimer through antiparallel beta-sheet augmentation via the beta2 strand of the protein. Structural comparison indicates that the two target peptides use different regions within the conformational flexible peptide-binding channels to achieve binding specificity. We have also re-determined the apo-form solution structure of DLC8 in this work. The structures of the DLC8/target peptide complexes, together with the dynamic properties of the protein, provide a molecular basis of DLC8's diverse amino acid sequence-dependent target recognition.

Selected figure(s)

Figure 3.
Figure 3. Comparison of the interactions of DLC8 with the Bim peptide and the nNOS peptide. Stereoview representations of (a) the Bim peptide; and (b) the nNOS peptide binding grooves of DLC8. For clarity, only the regions of DLC8 that are directly involved in the binding are included in the figure. In (a) and (b) the target pep- tides are shown using explicit atom representations in magenta. Amino acid residues in DLC8 that make key contacts with the peptides are also shown in the Figure. Due to its irregular strand structure, the b0 strand of DLC8 is also shown using explicit atom representations (yellow). (b) The distance between the oxygen atom of the Thr4 hydroxyl group of the nNOS pep- tide and the N e of His68 is also indicated. (c) Schematic showing the b-strand pairing between the b2 strand of DLC8 and the b strand of the nNOS peptide and the Bim peptide. The amino acid residues that adopt b-strand structure are highlighted by arrows. The amino acid residues in the b-strands with their side-chains pointing to the dimer interface are shaded.

Figure 6.
Figure 6. Identification of critical amino acid residues in the nNOS peptide for DLC8 binding. The amino acid sequence of the DLC8-binding region of the nNOS pep- tide (residues 1 to 12) is shown in the first row. Each mutation prepared in this study is shown in the sub- sequent rows. The DLC8-binding assay results, derived from the ``pull-down'' experiments, are shown at the right side of the Figure.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2001, 306, 97-0) copyright 2001.

Figures were selected by an automated process.