STRUCTURES, DYNAMICS AND INTERACTIONS OF EPHA5, EPHA7 AND NOGO-66 INVOLVED IN CNS REGNERATION INHIBITION

Abstract

CNS injuries usually lead to the permanent paralysis due to failure of axonal regeneration. 16 Eph kinases and their 9 ephrin ligands, have been investigated for their developmental roles in axon regeneration, axon guidance, topographic mapping etc. EphA5 is an axon guidance molecule and EphA7 is a tumor suppressor. To understand the structural basis underlying their diverse functions, crystal structures of EphA5 and EphA7 LBD was solved, followed by mapping their dynamic properties on different time scales, studying their interactions with peptides and compounds. Nogo-66 is an important region of Nogo proteins with multiple functions, especially in human CNS axonal regeneration inhibition. Fish Nogo-66 does not impair axon regeneration. Thus, the structure of its buffer-soluble form, Nogo-54 in Medaka fish was solved and compared with human Nogo-54. These findings may help in design and optimization of small ligands with high affinity and specificity for enhancing CNS regeneration and treating cancers.