PMID: 20133774

 

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Title : The protein tyrosine phosphatases PTPRZ and PTPRG bind to distinct members of the contactin family of neural recognition molecules

Abstract :

1. The receptor protein tyrosine phosphatases gamma ( PTPRG ) and zeta ( PTPRZ ) are expressed primarily in the nervous system and mediate cell adhesion and signaling events during development
2. We report here the crystal structures of the carbonic anhydrase-like domains of PTPRZ and PTPRG and show that these domains interact directly with the second and third immunoglobulin repeats of the members of the contactin ( CNTN ) family of neural recognition molecules
3. Interestingly, these receptors exhibit distinct specificities: PTPRZ binds only to CNTN1 , whereas PTPRG interacts with CNTN3 , 4, 5, and 6
4. Furthermore, we present crystal structures of the four N-terminal immunoglobulin repeats of mouse CNTN4 both alone and in complex with the carbonic anhydrase-like domain of mouse PTPRG
5. In these structures, the N-terminal region of CNTN4 adopts a horseshoe-like conformation found also in CNTN2 and most likely in all CNTNs.
6. This restrained conformation of the second and third immunoglobulin domains creates a binding site that is conserved among CNTN3 , 4, 5, and 6
7. This site contacts a discrete region of PTPRG composed primarily of an extended beta-hairpin loop found in both PTPRG and PTPRZ
8. Overall , these findings implicate PTPRG , PTPRZ and CNTNs as a group of receptors and ligands involved in the manifold recognition events that underlie the construction of neural networks