1hij

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1hij, resolution 3.00Å

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INTERLEUKIN-4 MUTANT WITH ARG 88 REPLACED WITH GLN (R88Q)

Contents

Overview

The structure of recombinant human interleukin-4 (hIL-4) has been, determined by both NMR and X-ray diffraction methods in several, laboratories, including ours. The X-ray and NMR structures were, successfully applied for solving the X-ray crystal structure by molecular, replacement. Due to the small size of the hIL-4 molecule (129 residues), and its lack of structural diversity (4-helix bundle), this task was, especially difficult and required special care with rotation function, applications. The crucial point was that proper removal of the Patterson, origin peaks was indispensable in all cases. All available structures of, hIL-4 were checked, in a standardized procedure, for their suitability as, templates for molecular replacement. The models derived from the various, structures are close to, but not in all loop details identical with, the, genuine X-ray structures. The deviations of the X-ray structure-derived, models are of the same magnitude as the differences between the original, X-ray structures, while the deviations of the NMR structure-derived models, are two to three times as large. The hIL-4 variant R88Q is a binding, mutant, its affinity to the receptor is decreased by a factor of about, 200. Its X-ray structure was determined by molecular replacement using the, wild-type X-ray structure determined in our laboratory as a model. The, structure of R88Q is virtually identical with that of the wild-type, protein. All differences besides the shortened side-chain of residue 88, occur at surface residues with high temperature factors, i.e. at spots, where the structure is not well defined. Since the structure is not, perturbed, the biological effect of decreased receptor affinity has to be, attributed to the loss of a single positive charge in the surface area of, the main receptor contact.

Disease

Known diseases associated with this structure: AIDS, slow progression to OMIM:[147781], Atopy, susceptibility to OMIM:[147781]

About this Structure

1HIJ is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Human interleukin-4 and variant R88Q: phasing X-ray diffraction data by molecular replacement using X-ray and nuclear magnetic resonance models., Muller T, Oehlenschlager F, Buehner M, J Mol Biol. 1995 Mar 24;247(2):360-72. PMID:7707380

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