The sema domain was first defined from sequence by Kolodkin and colleagues in the early 1990s, and constitutes the distinctive structural and functional element of semaphorins, their plexin receptors and the receptor tyrosine kinases MET and RON, three protein families with major roles in development, tissue regeneration and cancer. Recently determined crystal structures of two semaphorins (SEMA3A and SEMA4D) and the MET receptor have shown that the sema domain consists of a highly conserved variant form of the seven-blade beta-propeller fold. The structures, however, also suggest differences between these families with respect to the mode of dimerisation and the regions of the domain involved in ligand-receptor interactions. This reflects the considerable plasticity and adaptation of the sema domain in order to meet different binding requirements, properties that may underlie the vast array of ligand-receptor specificities and functions of the semaphorin superfamily.

Original publication

DOI

10.1016/j.sbi.2004.10.010

Type

Journal article

Journal

Curr Opin Struct Biol

Publication Date

12/2004

Volume

14

Pages

669 - 678

Keywords

Animals, Binding Sites, Humans, Models, Biological, Models, Chemical, Models, Molecular, Protein Binding, Protein Conformation, Protein Structure, Tertiary, Receptor Protein-Tyrosine Kinases, Semaphorins, Structure-Activity Relationship