Structural basis for nutrient acquisition by dominant members of the human gut microbiota

Amy J. Glenwright*, Karunakar R. Pothula*, Satya P. Bhamidimarri, Dror S. Chorev, Arnaud Baslé, Susan J. Firbank, Hongjun Zheng, Carol V. Robinson, Mathias Winterhalter, Ulrich Kleinekathöfer2, David N. Bolam & Bert van den Berg, Nature Letter 2017; 541, 407–411

Speaker: Chia-Yu Kang (康家瑜)                                         Time: 13:00~14:00, Apr. 26, 2017

Commentator: Dr. Shang-Rung Wu (吳尚蓉老師)              Place: Room 601

Abstract

Diverse and highly dense microbiota inhabits the human intestine. The distal gut microbiota is typically dominated by Gram negative phylum Bacteroidetes, which play an important role in human nutrient intake. One such attribute is their ability to degrade indigestible dietary glycans into products such as short-chain fatty acid that human can absorb¹. The genes encoding seven starch utilization proteins, SusA-SusG, involved in the glycan degradation coordinate polysaccharides utilization loci². This process depends on the import of oligosaccharides by outer membrane proteins. The outer membrane proteins are mainly composed of an extracellular SusD-like lipoprotein and integral membrane SusC-like TonB-dependent transporter (TBDT)³. However, the mechanism of extracellular substrate binding by SusD proteins though SusC transporter is unknown. In this study, the authors aim to 1) understand the mechanism of substrate acquisition by SusCD complexes using X-ray crystallography; and 2) draw the general molecular mechanism for multiple SusCD complexes in Bacteroides thetaiotaomicron by comparing the structure-function relationship of two different SusCD complexes. They further showed that in contrast to glycan uptake systems which express proteins to degrade glycan for uptake, the SusCD (BT2261-64) complex is expressed and functional only when the nutrient stress occurs. The structure of the SusCD complex was solved to 2.75 Å resolution reveals the homodimer assembly of SusC (BT2264) and an extracellular lid of SusD (BT2263) for transport mechanism. Therefore, the structure of SusCD reveals a ‘pedal bin’ mechanism, in which SusD moves away from SusC in a hinge loop L7 to expose the substrate binding site from external environment. These studies provide a mechanistic insight into outer membrane import by gut microbiota, an area of major importance for unknown human-microbiota symbiosis.

References

1     Martens, E. C., et al. Complex glycan catabolism by the human gut microbiota: the Bacteroidetes Sus-like paradigm. The Journal of biological chemistry 284, 24673-24677 (2009).

2.    Reeves, A. R., et al. Characterization of four outer membrane proteins that play a role in utilization of starch by Bacteroides thetaiotaomicron. Journal of bacteriology 179, 643-649 (1997).

3     Noinaj, N., et al. TonB-dependent transporters: regulation, structure, and function. Annual review of microbiology 64, 43-60 (2010).