Eph Receptor and Ephrin Cross-class Binding Activities
Open Access
Author:
Guo, Feiyi
Area of Honors:
Biochemistry and Molecular Biology
Degree:
Bachelor of Science
Document Type:
Thesis
Thesis Supervisors:
Arthur Mallay Lesk, Thesis Supervisor Chen Pei David Tu, Thesis Honors Advisor
Keywords:
Eph receptor ephrins cross-class binding
Abstract:
Eph receptors comprise the largest known family of receptor tyrosine kinases in mammals. They bind members of a second family, the ephrins. As both Eph receptors and ephrins are membrane bound, interactions permit bidirectional cell-cell signalling. Eph receptors and ephrins each form two classes, A and B, based on structures and patterns of affinity: Class A Eph receptors bind class A ephrins, and class B Eph receptors bind class B ephrins. The only known exceptions are EphA4, which can bind ephrinB21 and ephrinB3 in addition to the ephrin-As; and EphB2, which can bind ephrinA5 in addition to the ephrin-Bs.1 A crystal structure is available of the EphA4-ephrin B2 complex (wwPDB entry 2WO2). In this complex, the ligand-binding domain of EphA4 adopts an EphB-like conformation.2 To understand why other cross-class EphA receptor–ephrinB complexes do not form, we modeled hypothetical complexes between (1) EphA4–ephrinB1, (2) EphA4–ephrinB3, and (3) EphA2–ephrinB2. We identify particular residues in the interface region the size variations of which cause steric clashes that prevent formation of the unobserved complexes.
