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TitleCryo-EM of mammalian PA28αβ-iCP immunoproteasome reveals a distinct mechanism of proteasome activation by PA28αβ.
Journal, issue, pagesNat Commun, Vol. 12, Issue 1, Page 739, Year 2021
Publish dateFeb 2, 2021
AuthorsJinhuan Chen / Yifan Wang / Cong Xu / Kaijian Chen / Qiaoyu Zhao / Shutian Wang / Yue Yin / Chao Peng / Zhanyu Ding / Yao Cong /
PubMed AbstractThe 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, ...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 determine the spatial arrangement between PA28αβ and iCP through XL-MS. Our structures reveal a slight leaning of PA28αβ towards the α3-α4 side of iCP, disturbing the allosteric network of the gatekeeper α2/3/4 subunits, resulting in a partial open iCP gate. We find 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.
External linksNat Commun / PubMed:33531497 / PubMed Central
MethodsEM (single particle)
Resolution3.3 - 4.2 Å
Structure data

30824

7dr6

EMDB-30824, PDB-7dr6:
PA28alpha-beta in complex with immunoproteasome
Method: EM (single particle) / Resolution: 4.1 Å

30825

7dr7

EMDB-30825, PDB-7dr7:
bovine 20S immunoproteasome
Method: EM (single particle) / Resolution: 3.3 Å

30828

7drw

EMDB-30828, PDB-7drw:
Bovine 20S immunoproteasome in complex with two human PA28alpha-beta activators
Method: EM (single particle) / Resolution: 4.2 Å

Source
  • bos taurus (cattle)
  • homo sapiens (human)
KeywordsHYDROLASE / proteasome / PA28 alpha / PA28 beta / immunoproteasome / bovine spleen / PA28

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