PMID- 28894158
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20190404
LR  - 20190404
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 7
IP  - 1
DP  - 2017 Sep 11
TI  - Biophysical characterisation of the novel zinc binding property in Suppressor of 
      Fused.
PG  - 11139
LID - 10.1038/s41598-017-11203-2 [doi]
LID - 11139
AB  - Suppressor of Fused (SUFU) is a highly conserved protein that acts as a negative 
      regulator of the Hedgehog (HH) signalling pathway, a major determinant of cell 
      differentiation and proliferation. Therefore, SUFU deletion in mammals has 
      devastating effects on embryo development. SUFU is part of a multi-protein 
      cytoplasmic signal-transducing complex. Its partners include the Gli family of 
      transcription factors that function either as repressors, or as transcription 
      activators according to the HH activation state. The crystal structure of SUFU 
      revealed a two-domain arrangement, which undergoes a closing movement upon 
      binding a peptide from Gli1. There remains however, much to be discovered about 
      SUFU's behaviour. To this end, we expressed recombinant, full-length SUFU from 
      Drosophila, Zebrafish and Human. Guided by a sequence analysis that revealed a 
      conserved potential metal binding site, we discovered that SUFU binds zinc. This 
      binding was found to occur with a nanomolar affinity to SUFU from all three 
      species. Mutation of one histidine from the conserved motif induces a moderate 
      decrease in affinity for zinc, while circular dichroism indicates that the mutant 
      remains structured. Our results reveal new metal binding affinity characteristics 
      about SUFU that could be of importance for its regulatory function in HH.
FAU - Jabrani, Amira
AU  - Jabrani A
AD  - Laboratoire de Biologie Physico-Chimique des Proteines Membranaires, UMR 7099 
      CNRS, Universite Paris Diderot, Sorbonne Paris Cite, PSL Research University, 
      Institut de Biologie Physico-Chimique, 13 rue Pierre et Marie Curie, 75005, 
      Paris, France.
FAU - Makamte, Staelle
AU  - Makamte S
AD  - Laboratoire de Biologie Physico-Chimique des Proteines Membranaires, UMR 7099 
      CNRS, Universite Paris Diderot, Sorbonne Paris Cite, PSL Research University, 
      Institut de Biologie Physico-Chimique, 13 rue Pierre et Marie Curie, 75005, 
      Paris, France.
FAU - Moreau, Emilie
AU  - Moreau E
AD  - Laboratoire de Biologie Physico-Chimique des Proteines Membranaires, UMR 7099 
      CNRS, Universite Paris Diderot, Sorbonne Paris Cite, PSL Research University, 
      Institut de Biologie Physico-Chimique, 13 rue Pierre et Marie Curie, 75005, 
      Paris, France.
FAU - Gharbi, Yasmine
AU  - Gharbi Y
AD  - Laboratoire de Biologie Physico-Chimique des Proteines Membranaires, UMR 7099 
      CNRS, Universite Paris Diderot, Sorbonne Paris Cite, PSL Research University, 
      Institut de Biologie Physico-Chimique, 13 rue Pierre et Marie Curie, 75005, 
      Paris, France.
FAU - Plessis, Anne
AU  - Plessis A
AD  - Institut Jacques Monod UMR 7592, CNRS, Universite Paris Diderot, Sorbonne Paris 
      Cite, F-75205, Paris, France.
FAU - Bruzzone, Lucia
AU  - Bruzzone L
AD  - Institut Jacques Monod UMR 7592, CNRS, Universite Paris Diderot, Sorbonne Paris 
      Cite, F-75205, Paris, France.
FAU - Sanial, Matthieu
AU  - Sanial M
AD  - Institut Jacques Monod UMR 7592, CNRS, Universite Paris Diderot, Sorbonne Paris 
      Cite, F-75205, Paris, France.
FAU - Biou, Valerie
AU  - Biou V
AD  - Laboratoire de Biologie Physico-Chimique des Proteines Membranaires, UMR 7099 
      CNRS, Universite Paris Diderot, Sorbonne Paris Cite, PSL Research University, 
      Institut de Biologie Physico-Chimique, 13 rue Pierre et Marie Curie, 75005, 
      Paris, France. valerie.biou@ibpc.fr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170911
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
PMC - PMC5593987
COIS- The authors declare that they have no competing interests.
EDAT- 2017/09/13 06:00
MHDA- 2017/09/13 06:01
PMCR- 2017/09/11
CRDT- 2017/09/13 06:00
PHST- 2017/01/11 00:00 [received]
PHST- 2017/08/21 00:00 [accepted]
PHST- 2017/09/13 06:00 [entrez]
PHST- 2017/09/13 06:00 [pubmed]
PHST- 2017/09/13 06:01 [medline]
PHST- 2017/09/11 00:00 [pmc-release]
AID - 10.1038/s41598-017-11203-2 [pii]
AID - 11203 [pii]
AID - 10.1038/s41598-017-11203-2 [doi]
PST - epublish
SO  - Sci Rep. 2017 Sep 11;7(1):11139. doi: 10.1038/s41598-017-11203-2.