1q2h
From Proteopedia
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Phenylalanine Zipper Mediates APS Dimerization
Overview
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.
About this Structure
1Q2H is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
A phenylalanine zipper mediates APS dimerization., Dhe-Paganon S, Werner ED, Nishi M, Hansen L, Chi YI, Shoelson SE, Nat Struct Mol Biol. 2004 Oct;11(10):968-74. Epub 2004 Sep 19. PMID:15378031
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