1u5y

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File:1u5y.gif


1u5y, resolution 2.30Å

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Crystal structure of murine APRIL, pH 8.0

OverviewOverview

A proliferation-inducing ligand (APRIL) is a TNF-like cytokine that stimulates tumor cell growth. Within the TNF ligand superfamily, APRIL is most similar to B-cell activation factor (BAFF) with which it shares 30% sequence identity. APRIL binds the receptors B-cell maturation antigen (BCMA) and TACI with high affinity; both of these receptors have also been shown to bind BAFF, although BCMA has significantly higher affinity for APRIL than BAFF. Determination of the crystal structure of APRIL from three crystallization conditions at resolutions of 1.8-2.4A over a pH range from 5.0 to 8.5 reveals a compact trimeric ligand with a backbone fold very similar to that of BAFF (1.1A RMSD over 122 structurally equivalent Calpha atoms), with the exception of differences in the AA' and DE loop regions. Whereas BAFF has been shown to form 20-trimer assemblies under certain conditions, the molecular determinants required for BAFF-like assemblies are absent in the APRIL structure. No crystal packing suggestive of the formation of higher-order assemblies is seen in any of the crystal forms nor does the structure vary significantly between pH 5.0 and 8.5. Modeling of the APRIL-BCMA complex shows the resulting interface is in agreement with mutagenesis data.

About this StructureAbout this Structure

1U5Y is a Single protein structure of sequence from Mus musculus. Full crystallographic information is available from OCA.

ReferenceReference

The crystal structure of a proliferation-inducing ligand, APRIL., Wallweber HJ, Compaan DM, Starovasnik MA, Hymowitz SG, J Mol Biol. 2004 Oct 15;343(2):283-90. PMID:15451660

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