Dissecting the EphA3/ephrin-A5 interactions using a novel functional mutagenesis screen


Autoria(s): Smith, F. M.; Vearing, C.; Lackmann, M.; Treutlein, H.; Himanen, J.; Chen, K.; Saul, A.; Nikolov, D.; Boyd, A. W.
Contribuinte(s)

H. Tabor

Data(s)

01/01/2004

Resumo

The EphA3 receptor tyrosine kinase preferentially binds ephrin-A5, a member of the corresponding subfamily of membrane-associated ligands. Their interaction regulates critical cell communication functions in normal development and may play a role in neoplasia. Here we describe a random mutagenesis approach, which we employed to study the molecular determinants of the EphA3/ephrin-A5 recognition. Selection and functional characterization of EphA3 point mutants with impaired ephrin-A5 binding from a yeast expression library defined three EphA3 surface areas that are essential for the EphA3/ephrin-A5 interaction. Two of these map to regions identified previously in the crystal structure of the homologous EphB2-ephrin-B2 complex as potential ligand/receptor interfaces. In addition, we identify a third EphA3/ephrin-A5 interface that falls outside the structurally characterized interaction domains. Functional analysis of EphA3 mutants reveals that all three Eph/ephrin contact areas are essential for the assembly of signaling-competent, oligomeric receptor-ligand complexes.

Identificador

http://espace.library.uq.edu.au/view/UQ:69568

Idioma(s)

eng

Publicador

American Society for Biochemistry and Molecular Biology

Palavras-Chave #Biochemistry & Molecular Biology #Receptor Tyrosine Kinase #Eph Receptors #Ligand-binding #Crystal-structure #Hek #Dimerization #Attachment #Ephrins #Domain #C1 #321015 Oncology and Carcinogenesis #320305 Medical Biochemistry - Proteins and Peptides #730108 Cancer and related disorders
Tipo

Journal Article