Editors' ChoiceStructural Biology

Multimeric sTALL-1 Mimics a Virus

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Science's STKE  19 Feb 2002:
Vol. 2002, Issue 120, pp. tw76
DOI: 10.1126/stke.2002.120.tw76

Structural information is available about several members of the tumor necrosis factor (TNF) family members and, in some instances, regarding these ligands with their receptors. Liu et al. provide structural data for the sTALL-1 (also known as BAFF, THANK, Blys, and zTNF4) member of this family of proteins, which is implicated in inflammation, apoptosis, and organogenesis. Similar to other members of the TNF family, sTALL-1 formed trimers through conserved hydrophobic interactions. Unlike other TNF ligands, sTALL-1 formed higher order oligomeric structures (60 monomers interacting as 20 trimers, for example) that strongly resemble the assembled viral envelope of the satellite tobacco necrosis virus. These higher order oligomers were sensitive to pH and could be detected at pH 7.4, but not lower pH values, by gel filtration or electron microscopy. Mutations in the "flap" region disrupted the formation of the oligomers and destabilized the trimers. The mutated sTALL-1 bound to its receptor BMCA with affinity similar to that of the wild-type sTALL-1, but was defective in activating the receptor in two cellular assays. Liu et al. propose that the oligomeric sTALL-1 acts to promote the recruitment of multiple receptor trimers, which could result in amplification of downstream signaling. Sequence alignments with the other TNF family members suggest that the flap region may not be conserved; thus, sTALL-1 may be unique in forming these higher order structures.

Y. Liu, L. Xu, N. Opalka, J. Kappler, H.-B. Shu, G. Zhang, Crystal structure of sTALL-1 reveals a virus-like assembly of TNF family ligands. Cell 108, 383-394 (2002). [Online Journal]

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