PMID- 35378854
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220406
IS  - 2589-0042 (Electronic)
IS  - 2589-0042 (Linking)
VI  - 25
IP  - 4
DP  - 2022 Apr 15
TI  - Long-range structural preformation in yes-associated protein precedes encounter 
      complex formation with TEAD.
PG  - 104099
LID - 10.1016/j.isci.2022.104099 [doi]
LID - 104099
AB  - Yes-associated protein (YAP) is a partly intrinsically disordered protein (IDP) 
      that plays a major role as the downstream element of the Hippo pathway. Although 
      the structures of the complex between TEA domain transcription factors (TEADs) 
      and the TEAD-binding domain of YAP are already well characterized, its apo state 
      and the binding mechanism with TEADs are still not clearly defined. Here we 
      characterize via a combination of different NMR approaches with site-directed 
      mutagenesis and affinity measurements the intrinsically disordered solution state 
      of apo YAP. Our results provide evidence that the apo state of YAP adopts several 
      compact conformations that may facilitate the formation of the YAP:TEAD complex. 
      The interplay between local secondary structure element preformation and 
      long-range co-stabilization of these structured elements precedes the encounter 
      complex formation with TEAD and we, therefore, propose that TEAD binding proceeds 
      largely via conformational selection of the preformed compact substates 
      displaying at least nanosecond lifetimes.
CI  - (c) 2022 The Author(s).
FAU - Feichtinger, Michael
AU  - Feichtinger M
AD  - Department of Computational and Structural Biology, Max Perutz Labs, University 
      of Vienna, Campus Vienna Biocenter 5, 1030 Vienna, Austria.
FAU - Beier, Andreas
AU  - Beier A
AD  - Department of Computational and Structural Biology, Max Perutz Labs, University 
      of Vienna, Campus Vienna Biocenter 5, 1030 Vienna, Austria.
FAU - Migotti, Mario
AU  - Migotti M
AD  - Department of Computational and Structural Biology, Max Perutz Labs, University 
      of Vienna, Campus Vienna Biocenter 5, 1030 Vienna, Austria.
FAU - Schmid, Matthias
AU  - Schmid M
AD  - Department of Computational and Structural Biology, Max Perutz Labs, University 
      of Vienna, Campus Vienna Biocenter 5, 1030 Vienna, Austria.
FAU - Bokhovchuk, Fedir
AU  - Bokhovchuk F
AD  - Ichnos Sciences SA, Route de la Corniche 5A, 1066 Epalinges, Switzerland.
FAU - Chene, Patrick
AU  - Chene P
AD  - Novartis Pharma AG, Postfach WSJ 386.4, 4002 Basel, Switzerland.
FAU - Konrat, Robert
AU  - Konrat R
AD  - Department of Computational and Structural Biology, Max Perutz Labs, University 
      of Vienna, Campus Vienna Biocenter 5, 1030 Vienna, Austria.
LA  - eng
PT  - Journal Article
DEP - 20220317
PL  - United States
TA  - iScience
JT  - iScience
JID - 101724038
PMC - PMC8976148
OTO - NOTNLM
OT  - Biochemistry
OT  - Cell biology
OT  - Structural biology
COIS- The authors declare no competing interests.
EDAT- 2022/04/06 06:00
MHDA- 2022/04/06 06:01
PMCR- 2022/03/17
CRDT- 2022/04/05 05:12
PHST- 2021/10/14 00:00 [received]
PHST- 2022/01/25 00:00 [revised]
PHST- 2022/03/15 00:00 [accepted]
PHST- 2022/04/05 05:12 [entrez]
PHST- 2022/04/06 06:00 [pubmed]
PHST- 2022/04/06 06:01 [medline]
PHST- 2022/03/17 00:00 [pmc-release]
AID - S2589-0042(22)00369-8 [pii]
AID - 104099 [pii]
AID - 10.1016/j.isci.2022.104099 [doi]
PST - epublish
SO  - iScience. 2022 Mar 17;25(4):104099. doi: 10.1016/j.isci.2022.104099. eCollection 
      2022 Apr 15.