7TWD

Structure of AAGAB C-terminal dimerization domain

Summary for 7TWD

• Entry DOI: 10.2210/pdb7twd/pdb
• Descriptor: Alpha- and gamma-adaptin-binding protein p34, PHOSPHATE ION (3 entities in total)
• Functional Keywords: protein binding, membrane trafficking, ap complex, chaperone
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 10557.98

Authors

Tian, Y.,Yin, Q. (deposition date: 2022-02-07, release date: 2023-01-18, Last modification date: 2024-05-22)

Primary citation

Tian, Y.,Datta, I.,Yang, R.,Wan, C.,Wang, B.,Crisman, L.,He, H.,Brautigam, C.A.,Li, S.,Shen, J.,Yin, Q.
Oligomer-to-monomer transition underlies the chaperone function of AAGAB in AP1/AP2 assembly.
Proc.Natl.Acad.Sci.USA, 120:e2205199120-e2205199120, 2023

PubMed Abstract: 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 mutations. The oligomerization state transition mechanism may also underlie the functions of other assembly chaperones.

PubMed: 36598941
DOI: 10.1073/pnas.2205199120

Experimental method

X-RAY DIFFRACTION (2.11 Å)