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The crystal structure of a proliferation-inducing ligand, APRIL.

Abstract：

: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.

journal_name

J Mol Biol

journal_title

Journal of molecular biology

authors

Wallweber HJ,Compaan DM,Starovasnik MA,Hymowitz SG

doi

10.1016/j.jmb.2004.08.040

keywords:

subject

Has Abstract

pub_date

2004-10-15 00:00:00

pages

283-90

issue

2

eissn

0022-2836

issn

1089-8638

pii

S0022-2836(04)01020-4

journal_volume

343

pub_type

杂志文章

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