1QE6

INTERLEUKIN-8 WITH AN ADDED DISULFIDE BETWEEN RESIDUES 5 AND 33 (L5C/H33C)

Summary for 1QE6

• Entry DOI: 10.2210/pdb1qe6/pdb
• Related: 1ICW 3IL8
• Descriptor: INTERLEUKIN-8 VARIANT, SULFATE ION (3 entities in total)
• Functional Keywords: intercrine alpha family, immune system
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: P10145
• Total number of polymer chains: 4
• Total formula weight: 33715.34

Authors

Gerber, N.,Lowman, H.,Artis, D.R.,Eigenbrot, C. (deposition date: 1999-07-13, release date: 2000-03-22, Last modification date: 2024-11-20)

Primary citation

Gerber, N.,Lowman, H.,Artis, D.R.,Eigenbrot, C.
Receptor-binding conformation of the "ELR" motif of IL-8: X-ray structure of the L5C/H33C variant at 2.35 A resolution.
Proteins, 38:361-367, 2000

PubMed Abstract: The "ELR" (Glu-Leu-Arg) tripeptide sequence near the N-terminus of interleukin-8 (IL-8) contributes a large part of the receptor binding free energy. Prior X-ray and nuclear magnetic resonance (NMR) structures of IL-8 have shown this region of the molecule to be highly mobile. We reasoned that a hydrophobic interaction between the leucine and the neighboring beta-turn might exist in the receptor binding conformation of the N-terminus. To test this hypothesis, we mutated two residues to cysteine and connected the N-terminus to the beta-turn. The mutant retains receptor binding affinity reasonably close to wild type and allows the characterization of a high-affinity conformation that may be useful in the design of small IL-8 mimics. The L5C/H33C mutant is refined to R-values of R = 20.6% and Rfree = 27.7% at 2.35 A resolution. Other receptor binding determinants reside in the "N-loop" found after "ELR" and preceding the first beta-strand. All available structures of IL-8 have been found with one of two distinct N-loop conformations. One of these is relevant for receptor binding, based on NMR results with receptor peptides. The other conformation obscures the receptor-peptide binding surface and may have an undetermined but necessarily different function.

PubMed: 10707023
DOI: 10.1002/(SICI)1097-0134(20000301)38:4<361::AID-PROT2>3.3.CO;2-S

Experimental method

X-RAY DIFFRACTION (2.35 Å)