Turegun Bengi, Baker Richard W, Leschziner Andres E, Dominguez Roberto
Department of Physiology, Perelman School of Medicine, University of Pennsylvania, 728 Clinical Research Building, 415 Curie Boulevard, Philadelphia, PA, 19104-6085, USA.
Department of Cellular and Molecular Medicine, School of Medicine, and Section of Molecular Biology, Division of Biological Sciences, UC San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA.
Commun Biol. 2018;1:1. doi: 10.1038/s42003-017-0002-6. Epub 2018 Jan 22.
The catalytic subunits of SWI/SNF-family and INO80-family chromatin remodelers bind actin and actin-related proteins (Arps) through an N-terminal helicase/SANT-associated (HSA) domain. Between the HSA and ATPase domains lies a conserved post-HSA (pHSA) domain. The HSA domain of Sth1, the catalytic subunit of the yeast SWI/SNF-family remodeler RSC, recruits the Rtt102-Arp7/9 heterotrimer. Rtt102-Arp7/9 regulates RSC function, but the mechanism is unclear. We show that the pHSA domain interacts directly with another conserved region of the catalytic subunit, protrusion-1. Rtt102-Arp7/9 binding to the HSA domain weakens this interaction and promotes the formation of stable, monodisperse complexes with DNA and nucleosomes. A crystal structure of Rtt102-Arp7/9 shows that ATP binds to Arp7 but not Arp9. However, Arp7 does not hydrolyze ATP. Together, the results suggest that Rtt102 and ATP stabilize a conformation of Arp7/9 that potentiates binding to the HSA domain, which releases intramolecular interactions within Sth1 and controls DNA and nucleosome binding.
SWI/SNF家族和INO80家族染色质重塑因子的催化亚基通过N端解旋酶/SANT相关（HSA）结构域与肌动蛋白及肌动蛋白相关蛋白（Arp）结合。在HSA结构域和ATP酶结构域之间存在一个保守的HSA后（pHSA）结构域。酵母SWI/SNF家族重塑因子RSC的催化亚基Sth1的HSA结构域招募Rtt102-Arp7/9异源三聚体。Rtt102-Arp7/9调节RSC功能，但其机制尚不清楚。我们发现pHSA结构域直接与催化亚基的另一个保守区域——突出部-1相互作用。Rtt102-Arp7/9与HSA结构域的结合会削弱这种相互作用，并促进与DNA和核小体形成稳定的单分散复合物。Rtt102-Arp7/9的晶体结构表明ATP与Arp7结合但不与Arp9结合。然而，Arp7不水解ATP。综合这些结果表明，Rtt102和ATP稳定了Arp7/9的一种构象，这种构象增强了与HSA结构域的结合，从而释放了Sth1内的分子内相互作用并控制DNA和核小体的结合。
