6LAD

Crystal structure of Amuc_1100 from Akkermansia muciniphila

Summary for 6LAD

• Entry DOI: 10.2210/pdb6lad/pdb
• Descriptor: Amuc_1100 (2 entities in total)
• Functional Keywords: akkermansia muciniphila, outer-membrane protein, amuc_1100, type ii secretion system, toll-like receptor 2, membrane protein
• Biological source: Akkermansia muciniphila (strain ATCC BAA-835 / Muc)
• Total number of polymer chains: 6
• Total formula weight: 194116.17

Authors

Wang, J.,Xiang, R.,Zhang, M.,Wang, M. (deposition date: 2019-11-12, release date: 2020-08-05, Last modification date: 2024-03-27)

Primary citation

Wang, J.,Xiang, R.,Wang, R.,Zhang, B.,Gong, W.,Zhang, J.,Zhang, M.,Wang, M.
The variable oligomeric state of Amuc_1100 from Akkermansia muciniphila.
J.Struct.Biol., 212:107593-107593, 2020

PubMed Abstract: Akkermansia muciniphila is a beneficial microorganism colonized in the human gut that can reverse many intestinal metabolic-related diseases. Amuc_1100 is an outer-membrane protein of A. muciniphila. Oral administration of Amuc_1100 can reduce fat mass development, insulin resistance, and dyslipidemia in mice and activated the toll-like receptor 2 (TLR2) to regulate the immune response of the host, but the molecular mechanism remains unclear. Here we report the crystal structure of the extramembranous domain of Amuc_1100, which consists of a four-stranded antiparallel β-sheet and four α-helices. Two C-terminal helices and the four-stranded antiparallel β-sheet formed two "αββ" motifs and constituted the core domain, which shared a similar fold with type IV pili and type II Secretion system protein. Although the full-length of the extramembranous domain of Amuc_1100 existed as a monomer in solution, they formed trimer in the crystal. Elimination of the N-terminal coiled-coil helix α1 led to dimerization of Amuc_1100 both in solution and in crystal, indicating that the oligomeric state of Amuc_1100 was variable and could be influenced by α1. In addition, we identified that Amuc_1100 could directly bind human TLR2 (hTRL2) in vitro, suggesting that Amuc_1100 may serve as a new ligand for hTLR2. Dimerization of Amuc_1100 improved its hTLR2-binding affinity, suggesting that the α1-truncated Amuc_1100 could be a beneficial candidate for the development of A. muciniphila related drugs.

PubMed: 32736072
DOI: 10.1016/j.jsb.2020.107593

Experimental method

X-RAY DIFFRACTION (2.7 Å)