Crystal Structure of the Tandem Phosphatase Domains of RPTP LAR

Most receptor-like protein tyrosine phosphatases (RPTPs) contain two conserved phosphatase domains (D1 and D2) in their intracellular region. The carboxy-terminal D2 domain has little or no catalytic activity. The crystal structure of the tandem D1 and D2 domains of the human RPTP LAR revealed that...

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Bibliographic Details
Published in:Cell 1999-05, Vol.97 (4), p.449-457
Main Authors: Nam, Hyun-Joo, Poy, Florence, Krueger, Neil X, Saito, Haruo, Frederick, Christin A
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Binding Sites
Crystallography, X-Ray
Humans
Models, Molecular
Molecular Sequence Data
Mutagenesis
Protein Conformation
Protein Tyrosine Phosphatases - chemistry
Protein Tyrosine Phosphatases - genetics
Protein Tyrosine Phosphatases - metabolism
Receptor-Like Protein Tyrosine Phosphatases, Class 4
Receptors, Cell Surface
Sequence Homology, Amino Acid
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Summary:Most receptor-like protein tyrosine phosphatases (RPTPs) contain two conserved phosphatase domains (D1 and D2) in their intracellular region. The carboxy-terminal D2 domain has little or no catalytic activity. The crystal structure of the tandem D1 and D2 domains of the human RPTP LAR revealed that the tertiary structures of the LAR D1 and D2 domains are very similar to each other, with the exception of conformational differences at two amino acid positions in the D2 domain. Site-directed mutational changes at these positions (Leu-1644-to-Tyr and Glu-1779-to-Asp) conferred a robust PTPase activity to the D2 domain. The catalytic sites of both domains are accessible, in contrast to the dimeric blocked orientation model previously suggested. The relative orientation of the LAR D1 and D2 domains, constrained by a short linker, is stabilized by extensive interdomain interactions, suggesting that this orientation might be favored in solution.
ISSN:0092-8674
1097-4172
DOI:10.1016/S0092-8674(00)80755-2