Protein Name



Human (Homo sapiens)

Biological Context

F-spondin is a secreted and extracellular matrix-attached protein that has been implicated in axonal pathfinding during neural development as well as in vascular remodeling in adult tissues. F-spondin has 807 amino acids divided into eight domains: an N-terminal reeler domain, a spondin domain and six C-terminal thrombospondin type 1 repeat (TSR) domains. The N-terminal reeler domain of F-spondin shares amino acid sequence similarity with reelin, which is an extracellular matrix protein. F-spondin is processed in vivo to yield an amino half fragment that includes the reeler and spondin domains and a C-terminal fragment composed of TSR domains. Recent studies have shown that the N-terminal fragment binds to the central domain of amyloid precursor protein.

Structure Description


We have determined the crystal structures of two different constructs of the F-spondin reeler domain at 2.70 and 1.45 Å resolution, respectively. The crystal structure revealed that the reeler domain is composed of four- and five-stranded antiparallel β-sheets which together form a β-sandwich arrangement. The overall structural arrangement is similar to fibronectin type III or immunoglobulin domains. Structural comparisons of the F-spondin reeler domain using the DALI server resulted in a surprising top hit with the lumen-side domains of cytochrome f (PDB code: 1HCZ). However, the most unusual structural feature of the reeler domain is the presence of a highly mobile loop at the N-terminus. This loop is not a strand connecting loop nor does it protrude from the core antiparrallel β-sandvich. It is disulfide-bonded at one end and loosely wraps around the five-stranded antiparallel β-sheets. The mobile loop of the reeler domain is roughly situated at the two short helices of cytochrome f holding the redox-centre haem. Superposition of six reeler domain molecules in two constructs coincides well except for the conformation of the N-terminal loops. The temperature factors of the loop region are relatively high and the electron density of two out of six molecules in this region is ambiguous. Tan et al., also determined the crystal structure of F-spondin reeler domain and reported the structural flexibility in this mobile loop region. The overall domain fold of F-spondin reeler domain is unique in that one of the two outer faces of β-sandwich is covered by conserved loops, suggesting a specialized function of this face in mediating protein-protein interactions.

Protein Data Bank (PDB)



  • Nagae, M. Nishikawa, K. Yasui, N. Yamasaki, M. Nogi, T. Takagi, J.; "Structure of the F-spondin reeler domain reveals a unique beta-sandwich fold with a deformable disulfide-bonded loop"; Acta Crystallogr.,Sect.D; (2008) 64:1138-1145.
  • Tan, K., Duquette, M., Liu, J-H., Lawler, J., and Wang, J-H.; "The crystal structure of the heparin-binding reelin-N domain of f-spondin."; J. Mol. Biol.; (2008) 381:1213-1223.


author: Masamichi Nagae

Japanese version:PDB:2zot