1q2h
Phenylalanine Zipper Mediates APS Dimerization
Structural highlights
FunctionSH2B2_HUMAN Adapter protein for several members of the tyrosine kinase receptor family. Involved in multiple signaling pathways. May be involved in coupling from immunoreceptor to Ras signaling. Acts as a negative regulator of cytokine signaling in collaboration with CBL. Binds to EPOR and suppresses EPO-induced STAT5 activation, possibly through a masking effect on STAT5 docking sites in EPOR. Suppresses PDGF-induced mitogenesis. May induce cytoskeletal reorganization via interaction with VAV3.[1] [2] [3] [4] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe 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. 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[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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