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1: Nat Struct Mol Biol. 2004 Oct;11(10):968-74. Epub 2004 Sep 19.
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A phenylalanine zipper mediates APS dimerization.

Dhe-Paganon S, Werner ED, Nishi M, Hansen L, Chi YI, Shoelson SE.

Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA.

The APS, SH2-B and LNK proteins are adapters that activate and modulate receptor tyrosine kinase and JAK/STAT signaling. We now show that a conserved N-terminal domain mediates APS homodimerization. We determined the crystal structure of the dimerization domain at a resolution of 1.7 A using bromide ion MAD phasing. Each molecule contributes two helices to a compact four-helix bundle having a bisecting-U topology. Its most conspicuous feature is a stack of interdigitated phenylalanine side chains at the domain core. These residues create a new motif we refer to as a 'phenylalanine zipper,' which is critical to dimerization. A newly developed bridging yeast tri-hybrid assay showed that APS dimerizes JAK2, insulin receptor and IGF1 receptor kinases using its SH2 and dimerization domains. Dimerization via the phenylalanine zipper domain provides a mechanism for activating and modulating tyrosine kinase activity even in the absence of extracellular ligands.

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PMID: 15378031 [PubMed - indexed for MEDLINE]