6MFV

Crystal structure of the Signal Transduction ATPase with Numerous Domains (STAND) protein with a tetratricopeptide repeat sensor PH0952 from Pyrococcus horikoshii

Summary for 6MFV

• Entry DOI: 10.2210/pdb6mfv/pdb
• Descriptor: tetratricopeptide repeat sensor PH0952, ADENOSINE-5'-DIPHOSPHATE (2 entities in total)
• Functional Keywords: stand, nucleotide-binding oligomerization domain, tetratricopeptide, signal transduction, signaling protein
• Biological source: Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3)
• Total number of polymer chains: 4
• Total formula weight: 308122.02

Authors

Lisa, M.N.,Alzari, P.M.,Haouz, A.,Danot, O. (deposition date: 2018-09-12, release date: 2019-02-20, Last modification date: 2024-04-03)

Primary citation

Lisa, M.N.,Cvirkaite-Krupovic, V.,Richet, E.,Andre-Leroux, G.,Alzari, P.M.,Haouz, A.,Danot, O.
Double autoinhibition mechanism of signal transduction ATPases with numerous domains (STAND) with a tetratricopeptide repeat sensor.
Nucleic Acids Res., 47:3795-3810, 2019

PubMed Abstract: Upon triggering by their inducer, signal transduction ATPases with numerous domains (STANDs), initially in monomeric resting forms, multimerize into large hubs that activate target macromolecules. This process requires conversion of the STAND conserved core (the NOD) from a closed form encasing an ADP molecule to an ATP-bound open form prone to multimerize. In the absence of inducer, autoinhibitory interactions maintain the NOD closed. In particular, in resting STAND proteins with an LRR- or WD40-type sensor domain, the latter establishes interactions with the NOD that are disrupted in the multimerization-competent forms. Here, we solved the first crystal structure of a STAND with a tetratricopeptide repeat sensor domain, PH0952 from Pyrococcus horikoshii, revealing analogous NOD-sensor contacts. We use this structural information to experimentally demonstrate that similar interactions also exist in a PH0952 homolog, the MalT STAND archetype, and actually contribute to the MalT autoinhibition in vitro and in vivo. We propose that STAND activation occurs by stepwise release of autoinhibitory contacts coupled to the unmasking of inducer-binding determinants. The MalT example suggests that STAND weak autoinhibitory interactions could assist the binding of inhibitory proteins by placing in register inhibitor recognition elements born by two domains.

PubMed: 30788511
DOI: 10.1093/nar/gkz112

Experimental method

X-RAY DIFFRACTION (3.4 Å)