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PDBsum entry 1yfo
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Structural basis for inhibition of receptor protein-Tyrosine phosphatase-Alpha by dimerization.
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Authors
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A.M.Bilwes,
J.Den hertog,
T.Hunter,
J.P.Noel.
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Ref.
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Nature, 1996,
382,
555-559.
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PubMed id
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Abstract
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Receptor-like protein-tyrosine phosphatases (RPTPs), like their non-receptor
counterparts, regulate the level of phosphotyrosine-containing proteins derived
from the action of protein-tyrosine kinases. RPTPs are type-I integral membrane
proteins which contain one or two catalytic domains in their cytoplasmic region.
It is not known whether extracellular ligands regulate the activity of RPTPs.
Here we describe the crystal structure of the membrane-proximal catalytic domain
(D1) of a typical RPTP, murine RPTP alpha. Significant structural deviations
from the PTP1B fold reside within the amino-terminal helix-turn-helix segment of
RPTPalphaD1 (residues 214 to 242) and a distinctive two-stranded beta-sheet
formed between residues 211-213 and 458-461. The turn of the N-terminal segment
inserts into the active site of a dyad-related D1 monomer. On the basis of two
independent crystal structures, sequence alignments, and the reported biological
activity of EGF receptor/CD45 chimaeras, we propose that dimerization and
active-site blockage is a physiologically important mechanism for downregulating
the catalytic activity of RPTPalpha and other RPTPs.
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