Evidence for direct squalene and 2,3-oxidosqualene binding by supernatant protein factor

Christen, Monika; Marcaida, Maria; Lamprakis, Christos; Aeschimann, Walter; Vaithilingam, Jathana; Schneider, Petra; Hilbert, Manuel; Schneider, Gisbert; Cascella, Michele; Stocker, Achim (2015). Evidence for direct squalene and 2,3-oxidosqualene binding by supernatant protein factor. Journal of structural biology, 190(190), pp. 261-270. Elsevier 10.1016/j.jsb.2015.05.001

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We present the crystal structures of the SEC14-like domain of supernatant protein factor (SPF) in complex
with squalene and 2,3-oxidosqualene. The structures were resolved at 1.75 Å (complex with squalene)
and 1.6 Å resolution (complex with 2,3-oxidosqualene), leading in both cases to clear images of the protein/
substrate interactions. Ligand binding is facilitated by removal of the Golgi-dynamics (GOLD)
C-terminal domain of SPF, which, as shown in previous structures of the apo-protein, blocked the opening
of the binding pocket to the exterior. Both substrates bind into a large hydrophobic cavity, typical of such
lipid-transporter family. Our structures report no specific recognition mode for the epoxide group. In fact,
for both molecules, ligand affinity is dominated by hydrophobic interactions, and independent investigations
by computational models or differential scanning micro-calorimetry reveal similar binding affinities
for both ligands. Our findings elucidate the molecular bases of the role of SPF in sterol endo-synthesis,
supporting the original hypothesis that SPF is a facilitator of substrate flow within the sterol synthetic
pathway. Moreover, our results suggest that the GOLD domain acts as a regulator, as its conformational
displacement must occur to favor ligand binding and release during the different synthetic steps.

Item Type:

Journal Article (Original Article)


08 Faculty of Science > Department of Chemistry, Biochemistry and Pharmaceutical Sciences (DCBP)
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Social and Preventive Medicine (ISPM)

UniBE Contributor:

Marcaida, Maria, Lamprakis, Christos, Aeschimann, Walter, Vaithilingam, Jathana, Cascella, Michele, Stocker, Achim


500 Science > 570 Life sciences; biology
500 Science > 540 Chemistry
600 Technology > 610 Medicine & health
300 Social sciences, sociology & anthropology > 360 Social problems & social services








Achim Stocker

Date Deposited:

09 Nov 2015 15:44

Last Modified:

05 Dec 2022 14:49

Publisher DOI:






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