PDBsum entry 1q2h

Signaling protein

PDB id: 1q2h

Contents

Protein chains

63 a.a. *

Waters ×64

* Residue conservation analysis

PDB id:

1q2h

Name:

Signaling protein

Title:

Phenylalanine zipper mediates aps dimerization

Structure:

Adaptor protein with pleckstrin homology and src homology 2 domains. Chain: a, b, c. Synonym: aps. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: aps. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Biol. unit:

Dimer (from PDB file)

Resolution:

1.70Å R-factor: 0.250 R-free: 0.270

Authors:

S.Dhe-Paganon,E.D.Werner,M.Nishi,Y.-I.Chi,S.E.Shoelson

Key ref:

S.Dhe-Paganon et al. (2004). A phenylalanine zipper mediates APS dimerization. Nat Struct Mol Biol, 11, 968-974. PubMed id: 15378031 DOI: 10.1038/nsmb829

Date:

24-Jul-03 Release date: 03-Aug-04

Protein chains

O14492  (SH2B2_HUMAN) -  SH2B adapter protein 2 from Homo sapiens

Seq: 632 a.a.

Struc: 63 a.a.

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1038/nsmb829

Nat Struct Mol Biol 11:968-974 (2004)

PubMed id: 15378031

A phenylalanine zipper mediates APS dimerization.

S.Dhe-Paganon, E.D.Werner, M.Nishi, L.Hansen, Y.I.Chi, S.E.Shoelson.

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.

Selected figure(s)

Figure 1.
Figure 1. The APS/SH2-B/Lnk family. Schematic shows the domain organization of human APS, SH2-B and Lnk. Structure-based sequence alignment (below) is of the newly identified dimerization domain (DD). N- and C-terminal helices of the dimerization domain are identified above the sequences. Residues buried within the domain core are indicated with markers: phenylalanines within the zipper (Z) or paired at the ends of the domain (F), alanines in the trough (A), and other core residues (C).

Figure 3.
Figure 3. Crystal structure of the APS dimerization domain. Ribbon46 diagrams show the four-helix bundle formed from two molecules, colored green or red, in an atypical bisecting-U topology. Coils are brown and the -turns are blue. (a) Each molecule of the dimer contributes five phenylalanines to the phenylalanine zipper. (b) Paired phenylalanines also interact at the ends of the domain, and three alanines form a trough on the surfaces of the N-terminal helices.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Mol Biol (2004, 11, 968-974) copyright 2004.

Figures were selected by an automated process.