Oligomer-to-monomer transition underlies the chaperone function of AAGAB in AP1/AP2 assembly

Yuan Tian, Ishara Datta, Rui Yang, Chun Wan, Bing Wang, Lauren Crisman, Huan He, Chad A. Brautigam, Suzhao Li, Jingshi Shen, Qian Yin

Research output: Contribution to journalArticlepeer-review


Assembly of protein complexes is facilitated by assembly chaperones. Alpha and gamma adaptin-binding protein (AAGAB) is a chaperone governing the assembly of the heterotetrameric adaptor complexes 1 and 2 (AP1 and AP2) involved in clathrin-mediated membrane trafficking. Here, we found that before AP1/2 binding, AAGAB exists as a homodimer. AAGAB dimerization is mediated by its C-terminal domain (CTD), which is critical for AAGAB stability and is missing in mutant proteins found in patients with the skin disease punctate palmoplantar keratoderma type 1 (PPKP1). We solved the crystal structure of the dimerization-mediating CTD, revealing an antiparallel dimer of bent helices. Interestingly, AAGAB uses the same CTD to recognize and stabilize the γ subunit in the AP1 complex and the α subunit in the AP2 complex, forming binary complexes containing only one copy of AAGAB. These findings demonstrate a dual role of CTD in stabilizing resting AAGAB and binding to substrates, providing a molecular explanation for disease-causing AAGAB mutations. The oligomerization state transition mechanism may also underlie the functions of other assembly chaperones.

Original languageEnglish (US)
Article numbere2205199120
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number2
StatePublished - Jan 10 2023


  • adaptor complex
  • assembly chaperone
  • clathrin
  • membrane trafficking
  • oligomerization

ASJC Scopus subject areas

  • General


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