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The structure of the membrane distal phosphatase domain of RPTPalpha reveals interdomain flexibility and an SH2 domain interaction region.
- Source :
-
Biochemistry [Biochemistry] 2003 Jul 08; Vol. 42 (26), pp. 7904-14. - Publication Year :
- 2003
-
Abstract
- The receptor protein tyrosine phosphatase alpha (RPTPalpha) is a transmembrane receptor with two intracellular protein tyrosine phosphatase domains, a catalytically active membrane proximal domain (D1) and a membrane distal phosphatase domain with minimal catalytic activity (D2). Here we elucidate the crystal structure of RPTPalpha's D2 domain. Unlike D1, D2 exists as a monomer and lacks the N-terminal inhibitory wedge motif. The N-terminal portion of D2 is disordered, and this region linking D1 to D2 is proteolytically labile in solution whether part of D2 alone or tethered to D1, indicating that the polypeptide backbone of this part of D2 is highly flexible, and therefore accessible to proteases under native conditions. Furthermore, we have crystallized the SH2 domain of the protein tyrosine kinase c-Src, a RPTPalpha substrate, with a phosphopeptide encompassing the C-terminal phosphorylation site of D2 (pTyr789). The SH2 domain of Src binds RPTPalpha in an extended conformation. The structural and functional data support a D1-D2 arrangement with significant flexibility between phosphatase domains of RPTPalpha that is likely to be important for dynamic alterations in intra- and/or intermolecular interactions that are critical for RPTPalpha function.
- Subjects :
- Amino Acid Sequence
Animals
Catalytic Domain
DNA Primers chemistry
Escherichia coli genetics
Escherichia coli metabolism
Mice
Molecular Sequence Data
Phosphotyrosine
Plasmids
Polymerase Chain Reaction
Protein Binding
Protein Conformation
Protein Structure, Tertiary
Proto-Oncogene Proteins pp60(c-src) chemistry
Proto-Oncogene Proteins pp60(c-src) metabolism
Receptor-Like Protein Tyrosine Phosphatases, Class 4
Receptors, Cell Surface chemistry
Receptors, Cell Surface metabolism
Recombinant Proteins genetics
Recombinant Proteins isolation & purification
Recombinant Proteins metabolism
Sequence Homology, Amino Acid
src Homology Domains
Escherichia coli enzymology
Protein Tyrosine Phosphatases chemistry
Protein Tyrosine Phosphatases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0006-2960
- Volume :
- 42
- Issue :
- 26
- Database :
- MEDLINE
- Journal :
- Biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 12834342
- Full Text :
- https://doi.org/10.1021/bi0340503