7ALL

A single sulfatase is required for metabolism of colonic mucin O-glycans and intestinal colonization by a symbiotic human gut bacterium (BT4683-S1_4)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.63 Å
  • R-Value Free: 0.200 
  • R-Value Work: 0.174 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

A single sulfatase is required to access colonic mucin by a gut bacterium.

Luis, A.S.Jin, C.Pereira, G.V.Glowacki, R.W.P.Gugel, S.R.Singh, S.Byrne, D.P.Pudlo, N.A.London, J.A.Basle, A.Reihill, M.Oscarson, S.Eyers, P.A.Czjzek, M.Michel, G.Barbeyron, T.Yates, E.A.Hansson, G.C.Karlsson, N.G.Cartmell, A.Martens, E.C.

(2021) Nature 598: 332-337

  • DOI: 10.1038/s41586-021-03967-5
  • Primary Citation of Related Structures:  
    7ALL, 7AN1, 7ANA, 7ANB, 7OQD

  • PubMed Abstract: 
  • Humans have co-evolved with a dense community of microbial symbionts that inhabit the lower intestine. In the colon, secreted mucus creates a barrier that separates these microorganisms from the intestinal epithelium 1 . Some gut bacteria are able to utilize mucin glycoproteins, the main mucus component, as a nutrient source ...

    Humans have co-evolved with a dense community of microbial symbionts that inhabit the lower intestine. In the colon, secreted mucus creates a barrier that separates these microorganisms from the intestinal epithelium 1 . Some gut bacteria are able to utilize mucin glycoproteins, the main mucus component, as a nutrient source. However, it remains unclear which bacterial enzymes initiate degradation of the complex O-glycans found in mucins. In the distal colon, these glycans are heavily sulfated, but specific sulfatases that are active on colonic mucins have not been identified. Here we show that sulfatases are essential to the utilization of distal colonic mucin O-glycans by the human gut symbiont Bacteroides thetaiotaomicron. We characterized the activity of 12 different sulfatases produced by this species, showing that they are collectively active on all known sulfate linkages in O-glycans. Crystal structures of three enzymes provide mechanistic insight into the molecular basis of substrate specificity. Unexpectedly, we found that a single sulfatase is essential for utilization of sulfated O-glycans in vitro and also has a major role in vivo. Our results provide insight into the mechanisms of mucin degradation by a prominent group of gut bacteria, an important process for both normal microbial gut colonization 2 and diseases such as inflammatory bowel disease 3 .


    Organizational Affiliation

    Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI, USA. emartens@umich.edu.



Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChainsSequence LengthOrganismDetailsImage
ArylsulfataseA [auth AAA]523Bacteroides thetaiotaomicron VPI-5482Mutation(s): 1 
Gene Names: BT_4683
UniProt
Find proteins for Q89YP8 (Bacteroides thetaiotaomicron (strain ATCC 29148 / DSM 2079 / JCM 5827 / CCUG 10774 / NCTC 10582 / VPI-5482 / E50))
Explore Q89YP8 
Go to UniProtKB:  Q89YP8
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ89YP8
Protein Feature View
Expand
  • Reference Sequence
Oligosaccharides

Help

Entity ID: 2
MoleculeChainsChain Length2D DiagramGlycosylation3D Interactions
beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-alpha-D-glucopyranoseB [auth A]2N/A Oligosaccharides Interaction
Biologically Interesting Molecules (External Reference) 1 Unique
Entity ID: 2
IDChainsNameType/Class2D Diagram3D Interactions
PRD_900019
Query on PRD_900019
B [auth A]N-acetyl-alpha-lactosamineOligosaccharide / Glycan component Ligand Interaction
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.63 Å
  • R-Value Free: 0.200 
  • R-Value Work: 0.174 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 55.136α = 90
b = 87.799β = 90
c = 101.833γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
xia2data reduction
xia2data scaling
BALBESphasing

Structure Validation

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Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Wellcome TrustUnited KingdomSBF0051065163470

Revision History  (Full details and data files)

  • Version 1.0: 2021-10-13
    Type: Initial release
  • Version 1.1: 2021-11-03
    Changes: Data collection, Database references