Starch catabolism by a prominent human gut symbiont is directed by the recognition of amylose helices.
The human gut microbiota performs functions that are not encoded in our Homo sapiens genome, including the processing of otherwise undigestible dietary polysaccharides. Defining the structures of proteins involved in the import and degradation of specific glycans by saccharolytic bacteria complements genomic analysis of the nutrient-processing capabilities of gut communities. Here, we describe the atomic structure of one such protein, SusD, required for starch binding and utilization by Bacteroides thetaiotaomicron, a prominent adaptive forager of glycans in the distal human gut microbiota. The binding pocket of this unique alpha-helical protein contains an arc of aromatic residues that complements the natural helical structure of starch and imposes this conformation on bound maltoheptaose. Furthermore, SusD binds cyclic oligosaccharides with higher affinity than linear forms. The structures of several SusD/oligosaccharide complexes reveal an inherent ligand recognition plasticity dominated by the three-dimensional conformation of the oligosaccharides rather than specific interactions with the composite sugars.
Koropatkin
Nicole M
NM
Donald Danforth Plant Science Center, St. Louis, MO 63132, USA.
Martens
Eric C
EC
Gordon
Jeffrey I
JI
Smith
Thomas J
TJ
D000688:Amylose / Q000737:chemistry*; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry*; D001439:Bacteroides / Q000378:metabolism*; D001665:Binding Sites; D002151:Calorimetry; D002236:Carbohydrate Conformation; D041981:Gastrointestinal Tract / Q000382:microbiology; D005936:Glucans / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D009844:Oligosaccharides / Q000378:metabolism; D011485:Protein Binding; D013213:Starch / Q000737:chemistry / Q000378:metabolism*; D014312:Trisaccharides / Q000737:chemistry; D047392:beta-Cyclodextrins / Q000737:chemistry
D001425:Bacterial Outer Membrane Proteins; D005936:Glucans; D009844:Oligosaccharides; D014312:Trisaccharides; D047392:beta-Cyclodextrins; C021705:maltooligosaccharides; C031146:maltoheptaose; C008317:maltotriose; D013213:Starch; D000688:Amylose