1Q2H

Phenylalanine Zipper Mediates APS Dimerization

Summary for 1Q2H

• Entry DOI: 10.2210/pdb1q2h/pdb
• Descriptor: adaptor protein with pleckstrin homology and src homology 2 domains (2 entities in total)
• Functional Keywords: signal transduction, signaling protein
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: O14492
• Total number of polymer chains: 3
• Total formula weight: 23336.03

Authors

Dhe-Paganon, S.,Werner, E.D.,Nishi, M.,Chi, Y.-I.,Shoelson, S.E. (deposition date: 2003-07-24, release date: 2004-08-03, Last modification date: 2024-05-22)

Primary citation

Dhe-Paganon, S.,Werner, E.D.,Nishi, M.,Hansen, L.,Chi, Y.-I.,Shoelson, S.E.
A phenylalanine zipper mediates APS dimerization.
Nat.Struct.Mol.Biol., 11:968-974, 2004

PubMed Abstract: 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.

PubMed: 15378031
DOI: 10.1038/nsmb829

Experimental method

X-RAY DIFFRACTION (1.7 Å)