8AYR

Sialidases and Fucosidases of Akkermansia muciniphila are key for rapid growth on colonic mucin and nutrient sharing amongst mucin-associated human gut microbiota

Summary for 8AYR

• Entry DOI: 10.2210/pdb8ayr/pdb
• Descriptor: Coagulation factor 5/8 type domain protein, CALCIUM ION (3 entities in total)
• Functional Keywords: sialidase, neuraminidase, hydrolase
• Biological source: Akkermansia muciniphila
• Total number of polymer chains: 2
• Total formula weight: 155553.95

Authors

Sakanaka, H.,Nielsen, T.S.,Pichler, M.J.,Nordberg Karlsson, E.,Abou Hachem, M.,Morth, J.P. (deposition date: 2022-09-02, release date: 2023-03-01, Last modification date: 2024-05-01)

Primary citation

Shuoker, B.,Pichler, M.J.,Jin, C.,Sakanaka, H.,Wu, H.,Gascuena, A.M.,Liu, J.,Nielsen, T.S.,Holgersson, J.,Nordberg Karlsson, E.,Juge, N.,Meier, S.,Morth, J.P.,Karlsson, N.G.,Abou Hachem, M.
Sialidases and fucosidases of Akkermansia muciniphila are crucial for growth on mucin and nutrient sharing with mucus-associated gut bacteria.
Nat Commun, 14:1833-1833, 2023

PubMed Abstract: The mucolytic human gut microbiota specialist Akkermansia muciniphila is proposed to boost mucin-secretion by the host, thereby being a key player in mucus turnover. Mucin glycan utilization requires the removal of protective caps, notably fucose and sialic acid, but the enzymatic details of this process remain largely unknown. Here, we describe the specificities of ten A. muciniphila glycoside hydrolases, which collectively remove all known sialyl and fucosyl mucin caps including those on double-sulfated epitopes. Structural analyses revealed an unprecedented fucosidase modular arrangement and explained the sialyl T-antigen specificity of a sialidase of a previously unknown family. Cell-attached sialidases and fucosidases displayed mucin-binding and their inhibition abolished growth of A. muciniphila on mucin. Remarkably, neither the sialic acid nor fucose contributed to A. muciniphila growth, but instead promoted butyrate production by co-cultured Clostridia. This study brings unprecedented mechanistic insight into the initiation of mucin O-glycan degradation by A. muciniphila and nutrient sharing between mucus-associated bacteria.

PubMed: 37005422
DOI: 10.1038/s41467-023-37533-6

Experimental method

X-RAY DIFFRACTION (2.7 Å)