The Olfactomedin Domain from Gliomedin Is a β-Propeller with Unique Structural Properties

Abstract

Background: Gliomedin contains an olfactomedin (OLF) domain, for which structural information has been lacking. Results: The crystal structure of the OLF domain from gliomedin was solved. Conclusion:The OLF domain is a five-bladed ␤-propeller with broken symmetry. Significance: The results provide a structural basis for gliomedin function and shed light on mutations in the human OLF family.

Structural Basis of Latrophilin-FLRT-UNC5 Interaction in Cell Adhesion

“…The blades of the olfactomedin domain are asymmetrical, and the fifth blade from where the N- and C-termini emerge is larger than the other blades, spanning as much space as almost two blades. This type of beta-propeller structure was recently observed in the structure of olfactomedin domain of gliomedin as well (Han and Kursula, 2015). …”

Structural and Mechanistic Insights into the Latrophilin3-FLRT3 Complex that Mediates Glutamatergic Synapse Development

“…Our LPHN3-OLF structure is very similar to several other OLF domain structures recently determined from LPHN3 (the mouse LPHN3 lectin and olfactomedin-like domains (LPHN3-RBL/OLF)) (Jackson et al, 2015), gliomedin (gliomedin-OLF) (Han and Kursula, 2015), myocilin (myocilin-OLF) (Donegan et al, 2014) and noelin (noelin-OLF) (Pronker et al, 2015) (Table S2, related to Figure 2). Consistently, our LPHN3-OLF structure displays a five-bladed β-propeller folding, i.e.…”

“…Some conformational motion of the myocilin-OLF equivalent loop B-10/C-11 has been reported when comparing the polyethylene glycol-containing wild type structure to the glycerol-containing form or to the SeMet derivative form of the E396D mutant (Donegan et al, 2014). Gliomedin-OLF appears to be different in this respect, since the LPHN3-OLF Tyr323-Asp332-Ca 2+ trio structurally superimposes with Phe415-Asn423-Na + (Figure S1D, related to figure 2), however, the gliomedin-OLF 407–420 loop (equivalent to LPHN3-OLF 316–329) is poorly conserved (Han and Kursula, 2015). The fact that Phe415 and the proximal Leu414 are involved in a core-buried hydrophobic cluster suggests that the entire loop is less dynamic.…”

“…The most extensively studied OLF-containing protein is probably myocilin in which mutations are found in more than 10% of juvenile open-angle glaucoma cases and in 3–4% of patients with adult onset primary open-angle glaucoma (POAG) (Fingert et al, 1999; Stone et al, 1997). The available crystal structures of gliomedin and myocilin, two members of the OLF family reveal a 5-blade β-propeller fold and the presence of Ca 2+ and/or Na + in the central pore (Donegan et al, 2014; Han and Kursula, 2015). Recent findings on the extracellular domain of FLRT3 reveal that this protein has the tendency to homo-dimerize but a precise characterization of dimerization potential is currently unknown.…”

Internal symmetry in protein structures: prevalence, functional relevance and evolution

“…Can we comprehensively delineate the relationship between internal symmetry and function, stability and folding? Can we broaden the definition of internal symmetry to include more imperfect symmetries found within protein structures such as the recently determined structure of olfactomedin domain from gliomedin [59]? Can we recalibrate protein functions or interactions by altering the symmetric nature of a given fold?…”