7RFQ

STRUCTURE OF BACTERIAL SYLF DOMAIN CONTAINING PROTEIN, BETA CELL EXPANSION FACTOR A (BEFA)

Summary for 7RFQ

• Entry DOI: 10.2210/pdb7rfq/pdb
• Descriptor: BETA CELL EXPANSION FACTOR A (BEFA), CITRIC ACID (3 entities in total)
• Functional Keywords: sylf domain, bacterial protein, developmental regulator, beta cell expansion factor, signaling protein
• Biological source: Aeromonas veronii
• Total number of polymer chains: 1
• Total formula weight: 30223.09

Authors

Sweeney, E.G. (deposition date: 2021-07-14, release date: 2022-07-20, Last modification date: 2024-05-22)

Primary citation

Hill, J.H.,Massaquoi, M.S.,Sweeney, E.G.,Wall, E.S.,Jahl, P.,Bell, R.,Kallio, K.,Derrick, D.,Murtaugh, L.C.,Parthasarathy, R.,Remington, S.J.,Round, J.L.,Guillemin, K.
BefA, a microbiota-secreted membrane disrupter, disseminates to the pancreas and increases beta cell mass.
Cell Metab., 34:1779-1791.e9, 2022

PubMed Abstract: Microbiome dysbiosis is a feature of diabetes, but how microbial products influence insulin production is poorly understood. We report the mechanism of BefA, a microbiome-derived protein that increases proliferation of insulin-producing β cells during development in gnotobiotic zebrafish and mice. BefA disseminates systemically by multiple anatomic routes to act directly on pancreatic islets. We detail BefA's atomic structure, containing a lipid-binding SYLF domain, and demonstrate that it permeabilizes synthetic liposomes and bacterial membranes. A BefA mutant impaired in membrane disruption fails to expand β cells, whereas the pore-forming host defense protein, Reg3, stimulates β cell proliferation. Our work demonstrates that membrane permeabilization by microbiome-derived and host defense proteins is necessary and sufficient for β cell expansion during pancreas development, potentially connecting microbiome composition with diabetes risk.

PubMed: 36240759
DOI: 10.1016/j.cmet.2022.09.001

Experimental method

X-RAY DIFFRACTION (1.27 Å)