A large disordered region confers a wide spanning volume to vertebrate Suppressor of Fused as shown in a trans-species solution study - Institut Jacques Monod Accéder directement au contenu
Article Dans Une Revue Journal of Structural Biology Année : 2022

A large disordered region confers a wide spanning volume to vertebrate Suppressor of Fused as shown in a trans-species solution study

Résumé

Hedgehog (Hh) pathway inhibition by the conserved protein Suppressor of Fused (SuFu) is crucial to vertebrate development. By constrast, SuFu removal has little effect in drosophila. Previous publications showed that the crystal structures of human and drosophila SuFu consist of two ordered domains that are capable of breathing motions upon ligand binding. However, the crystal structure of human SuFu does not give information about 20 N-terminal residues (IDR1) and an eighty-residue-long disordered region (IDR2) in the C-terminus, whose function is important for the pathway repression. These two IDRs are species-dependent. We studied SuFu’s structure in solution, both with circular dichroism and small angle X-ray scattering, comparing drosophila, zebrafish and human species, to better understand this considerable difference. Our studies show that, in spite of similar crystal structures restricted to ordered domains, drosophila and vertebrate SuFu have very different structures in solution. The IDR2 of vertebrates spans a large area, thus enabling it to reach for partners and be accessible for post-translational modifications. Furthermore, we show that the IDR2 region is highly conserved within phyla but varies in length and sequence, with insects having a shorter disordered region while that of vertebrates is broad and mobile. This major variation may explain the different phenotypes observed upon SuFu removal.
Fichier principal
Vignette du fichier
Makamte_SufuJstructBiol2022.pdf (3.47 Mo) Télécharger le fichier
Origine : Publication financée par une institution

Dates et versions

hal-03413156 , version 1 (17-11-2022)

Identifiants

Citer

Staëlle Makamte, Aurélien Thureau, Amira Jabrani, Annick Paquelin, Anne Plessis, et al.. A large disordered region confers a wide spanning volume to vertebrate Suppressor of Fused as shown in a trans-species solution study. Journal of Structural Biology, 2022, 214 (2), pp.107853. ⟨10.1016/j.jsb.2022.107853⟩. ⟨hal-03413156⟩
53 Consultations
15 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More