Cryo-EM of mammalian PA28αβ-iCP immunoproteasome reveals a distinct mechanism of proteasome activation by PA28αβ
Jinhuan Chen, Yifan Wang, Cong Xu, Chao Peng, Zhanyu Ding, Yao Cong
Received Date: 12th May 20
The proteasome activator PA28αβ affects MHC class-I antigen presentation by associating with immunoproteasome core particles (iCPs). However, due to the lack of a mammalian PA28αβ-iCP structure, how PA28αβ regulates proteasome remains elusive. Here we present the complete architectures of the mammalian PA28αβ-iCP immunoproteasome and free iCP at near atomic-resolution by cryo-EM, and determined the spatial arrangement between PA28αβ and iCP through XL-MS. Our structures revealed a slight leaning of PA28αβ towards the a3-a4 side of iCP, disturbing the allosteric network of the gate-keeper a2/3/4 subunits, resulting in a partial open iCP gate. We found that the binding and activation mechanism of iCP by PA28αβ is distinct from those of constitutive CP by the homoheptameric TbPA26 or PfPA28. Our study sheds lights on the mechanism of enzymatic activity stimulation of immunoproteasome and suggests that PA28αβ-iCP has experienced profound remodeling during evolution to achieve its current level of function in immune response.
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This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.