Desantis Morgan E, Shorter James
Department of Biochemistry and Biophysics, Perelman School of Medicine at The University of Pennsylvania, 805b Stellar-Chance Laboratories, 422 Curie Boulevard, Philadelphia, PA 19104, USA.
Biochim Biophys Acta. 2012 Jan;1823(1):29-39. doi: 10.1016/j.bbamcr.2011.07.014. Epub 2011 Jul 24.
Hsp104 in yeast and ClpB in bacteria are homologous, hexameric AAA+ proteins and Hsp100 chaperones, which function in the stress response as ring-translocases that drive protein disaggregation and reactivation. Both Hsp104 and ClpB contain a distinctive coiled-coil middle domain (MD) inserted in the first AAA+ domain, which distinguishes them from other AAA+ proteins and Hsp100 family members. Here, we focus on recent developments concerning the location and function of the MD in these hexameric molecular machines, which remains an outstanding question. While the atomic structure of the hexameric assembly of Hsp104 and ClpB remains uncertain, recent advances have illuminated that the MD is critical for the intrinsic disaggregase activity of the hexamer and mediates key functional interactions with the Hsp70 chaperone system (Hsp70 and Hsp40) that empower protein disaggregation.
酵母中的Hsp104和细菌中的ClpB是同源的六聚体AAA+蛋白及Hsp100伴侣蛋白，它们在应激反应中作为驱动蛋白质解聚和再激活的环状转位酶发挥作用。Hsp104和ClpB都含有一个独特的卷曲螺旋中间结构域（MD），该结构域插入到第一个AAA+结构域中，这使它们有别于其他AAA+蛋白和Hsp100家族成员。在此，我们聚焦于关于MD在这些六聚体分子机器中的位置和功能的最新进展，这仍是一个悬而未决的问题。虽然Hsp104和ClpB六聚体组装体的原子结构尚不确定，但最近的进展表明，MD对于六聚体的内在解聚酶活性至关重要，并介导与Hsp70伴侣系统（Hsp70和Hsp40）的关键功能相互作用，从而促进蛋白质解聚。
