PMID- 35364288
OWN - NLM
STAT- MEDLINE
DCOM- 20220531
LR  - 20220613
IS  - 1095-8657 (Electronic)
IS  - 1047-8477 (Linking)
VI  - 214
IP  - 2
DP  - 2022 Jun
TI  - A large disordered region confers a wide spanning volume to vertebrate Suppressor 
      of Fused as shown in a trans-species solution study.
PG  - 107853
LID - S1047-8477(22)00023-5 [pii]
LID - 10.1016/j.jsb.2022.107853 [doi]
AB  - Hedgehog (Hh) pathway inhibition by the conserved protein Suppressor of Fused 
      (SuFu) is crucial to vertebrate development. By constrast, SuFu loss-of-function 
      mutant 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 twenty N-terminal 
      residues (IDR1) and an eighty-residue-long region predicted as disordered (IDR2) 
      in the C-terminus, whose function is important for the pathway repression. These 
      two intrinsically disordered regions (IDRs) are species-dependent. To obtain 
      information about the IDR regions, we studied full-length 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.
CI  - Copyright (c) 2022 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Makamte, Staelle
AU  - Makamte S
AD  - Laboratoire de Biologie Physico-Chimique des Proteines Membranaires, Universite 
      de Paris, UMR 7099 CNRS, Institut de Biologie Physico-Chimique, 13 rue Pierre et 
      Marie Curie, 75005 Paris, France.
FAU - Thureau, Aurelien
AU  - Thureau A
AD  - Synchrotron SOLEIL, F-91192 Gif sur Yvette, France.
FAU - Jabrani, Amira
AU  - Jabrani A
AD  - Laboratoire de Biologie Physico-Chimique des Proteines Membranaires, Universite 
      de Paris, UMR 7099 CNRS, Institut de Biologie Physico-Chimique, 13 rue Pierre et 
      Marie Curie, 75005 Paris, France.
FAU - Paquelin, Annick
AU  - Paquelin A
AD  - Laboratoire de Biologie Physico-Chimique des Proteines Membranaires, Universite 
      de Paris, UMR 7099 CNRS, Institut de Biologie Physico-Chimique, 13 rue Pierre et 
      Marie Curie, 75005 Paris, France.
FAU - Plessis, Anne
AU  - Plessis A
AD  - Universite de Paris, CNRS, Institut Jacques Monod, F-75006 Paris, France.
FAU - Sanial, Matthieu
AU  - Sanial M
AD  - Universite de Paris, CNRS, Institut Jacques Monod, F-75006 Paris, France.
FAU - Rudenko, Olga
AU  - Rudenko O
AD  - Synchrotron SOLEIL, F-91192 Gif sur Yvette, France.
FAU - Oteri, Francesco
AU  - Oteri F
AD  - Laboratoire de Biochimie Theorique, UPR 9080 CNRS, Institut de Biologie 
      Physico-Chimique, 13 rue Pierre et Marie Curie, 75005 Paris, France.
FAU - Baaden, Marc
AU  - Baaden M
AD  - Laboratoire de Biochimie Theorique, UPR 9080 CNRS, Institut de Biologie 
      Physico-Chimique, 13 rue Pierre et Marie Curie, 75005 Paris, France.
FAU - Biou, Valerie
AU  - Biou V
AD  - Laboratoire de Biologie Physico-Chimique des Proteines Membranaires, Universite 
      de Paris, UMR 7099 CNRS, Institut de Biologie Physico-Chimique, 13 rue Pierre et 
      Marie Curie, 75005 Paris, France. Electronic address: valerie.biou@ibpc.fr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220329
PL  - United States
TA  - J Struct Biol
JT  - Journal of structural biology
JID - 9011206
RN  - 0 (Hedgehog Proteins)
RN  - 0 (Repressor Proteins)
SB  - IM
MH  - Animals
MH  - Drosophila/genetics
MH  - *Hedgehog Proteins/genetics
MH  - *Repressor Proteins/chemistry
MH  - Signal Transduction/genetics
MH  - Zebrafish
OTO - NOTNLM
OT  - Hedgehog signal
OT  - Intrinsically disordered protein
OT  - Small-angle X-ray scattering
EDAT- 2022/04/02 06:00
MHDA- 2022/06/01 06:00
CRDT- 2022/04/01 20:11
PHST- 2021/11/12 00:00 [received]
PHST- 2022/03/10 00:00 [revised]
PHST- 2022/03/24 00:00 [accepted]
PHST- 2022/04/02 06:00 [pubmed]
PHST- 2022/06/01 06:00 [medline]
PHST- 2022/04/01 20:11 [entrez]
AID - S1047-8477(22)00023-5 [pii]
AID - 10.1016/j.jsb.2022.107853 [doi]
PST - ppublish
SO  - J Struct Biol. 2022 Jun;214(2):107853. doi: 10.1016/j.jsb.2022.107853. Epub 2022 
      Mar 29.