4EZX

Crystal structure of the substrate binding domain of E.coli DnaK in complex with the designer peptide NRLMLTG

Summary for 4EZX

• Entry DOI: 10.2210/pdb4ezx/pdb
• Related: 1DKX 1DKY 1DKZ 3DPO 3DPP 3DPQ 3QNJ 4E81 4EZN 4EZO 4EZP 4EZQ 4EZR 4EZS 4EZT 4EZU 4EZV 4EZW 4EZY 4EZZ 4F00 4F01
• Descriptor: Chaperone protein DnaK, synthetic peptide NRLMLTG, SULFATE ION, ... (4 entities in total)
• Functional Keywords: chaperone, chaperone-peptide binding protein complex, chaperone/peptide binding protein
• Biological source: Escherichia coli; More
• Cellular location: Cytoplasm : P0A6Y8
• Total number of polymer chains: 4
• Total formula weight: 49731.83

Authors

Zahn, M.,Straeter, N. (deposition date: 2012-05-03, release date: 2013-04-17, Last modification date: 2024-02-28)

Primary citation

Zahn, M.,Berthold, N.,Kieslich, B.,Knappe, D.,Hoffmann, R.,Strater, N.
Structural Studies on the Forward and Reverse Binding Modes of Peptides to the Chaperone DnaK.
J.Mol.Biol., 425:2463-2479, 2013

PubMed Abstract: Hsp70 chaperones have been implicated in assisting protein folding of newly synthesized polypeptide chains, refolding of misfolded proteins, and protein trafficking. For these functions, the chaperones need to exhibit a significant promiscuity in binding to different sequences of hydrophobic peptide stretches. To characterize the structural basis of sequence specificity and flexibility of the Escherichia coli Hsp70 chaperone DnaK, we have analyzed crystal structures of the substrate binding domain of the protein in complex with artificially designed peptides as well as small proline-rich antimicrobial peptides. The latter peptides from mammals and insects were identified to target DnaK after cell penetration. Interestingly, the complex crystal structures reveal two different peptide binding modes. The peptides can bind either in a forward or in a reverse direction to the conventional substrate binding cleft of DnaK in an extended conformation. Superposition of the two binding modes shows a remarkable similarity in the side chain orientations and hydrogen bonding pattern despite the reversed peptide orientation. The DnaK chaperone has evolved to bind peptides in both orientations in the substrate binding cleft with comparable energy without rearrangements of the protein. Optimal hydrophobic interactions with binding pockets -2 to 0 appear to be the main determinant for the orientation and sequence position of peptide binding.

PubMed: 23562829
DOI: 10.1016/j.jmb.2013.03.041

Experimental method

X-RAY DIFFRACTION (1.7 Å)