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BMC Bioinformatics. 2015 Jan 16;16:7. doi: 10.1186/s12859-014-0434-7.

Structure and sequence analyses of Bacteroides proteins BVU_4064 and BF1687 reveal presence of two novel predominantly-beta domains, predicted to be involved in lipid and cell surface interactions.

Author information

1
Joint Center for Structural Genomics, San Diego, USA. pnatarajan@sanfordburnham.org.
2
Program on Bioinformatics and Systems Biology, Sanford-Burnham Medical Research Institute, La Jolla, CA, USA. pnatarajan@sanfordburnham.org.
3
European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SD, UK. mpunta@ebi.ac.uk.
4
Joint Center for Structural Genomics, San Diego, USA. abhinavk@slac.stanford.edu.
5
Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Menlo Park, CA, 94025, USA. abhinavk@slac.stanford.edu.
6
Joint Center for Structural Genomics, San Diego, USA. Andrew.P.Yeh@gmail.com.
7
Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Menlo Park, CA, 94025, USA. Andrew.P.Yeh@gmail.com.
8
Joint Center for Structural Genomics, San Diego, USA. adam@sanfordburnham.org.
9
Program on Bioinformatics and Systems Biology, Sanford-Burnham Medical Research Institute, La Jolla, CA, USA. adam@sanfordburnham.org.
10
National Center for Biotechnology Information, National Library of Medicine, Building 38A, Bethesda, MD, 20894, USA. aravind@ncbi.nlm.nih.gov.

Abstract

BACKGROUND:

N-terminal domains of BVU_4064 and BF1687 proteins from Bacteroides vulgatus and Bacteroides fragilis respectively are members of the Pfam family PF12985 (DUF3869). Proteins containing a domain from this family can be found in most Bacteroides species and, in large numbers, in all human gut microbiome samples. Both BVU_4064 and BF1687 proteins have a consensus lipobox motif implying they are anchored to the membrane, but their functions are otherwise unknown. The C-terminal half of BVU_4064 is assigned to protein family PF12986 (DUF3870); the equivalent part of BF1687 was unclassified.

RESULTS:

Crystal structures of both BVU_4064 and BF1687 proteins, solved at the JCSG center, show strikingly similar three-dimensional structures. The main difference between the two is that the two domains in the BVU_4064 protein are connected by a short linker, as opposed to a longer insertion made of 4 helices placed linearly along with a strand that is added to the C-terminal domain in the BF1687 protein. The N-terminal domain in both proteins, corresponding to the PF12985 (DUF3869) domain is a β-sandwich with pre-albumin-like fold, found in many proteins belonging to the Transthyretin clan of Pfam. The structures of C-terminal domains of both proteins, corresponding to the PF12986 (DUF3870) domain in BVU_4064 protein and an unclassified domain in the BF1687 protein, show significant structural similarity to bacterial pore-forming toxins. A helix in this domain is in an analogous position to a loop connecting the second and third strands in the toxin structures, where this loop is implicated to play a role in the toxin insertion into the host cell membrane. The same helix also points to the groove between the N- and C-terminal domains that are loosely held together by hydrophobic and hydrogen bond interactions. The presence of several conserved residues in this region together with these structural determinants could make it a functionally important region in these proteins.

CONCLUSIONS:

Structural analysis of BVU_4064 and BF1687 points to possible roles in mediating multiple interactions on the cell-surface/extracellular matrix. In particular the N-terminal domain could be involved in adhesive interactions, the C-terminal domain and the inter-domain groove in lipid or carbohydrate interactions.

PMID:
25592227
PMCID:
PMC4387736
DOI:
10.1186/s12859-014-0434-7
[Indexed for MEDLINE]
Free PMC Article

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