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Filling out the structural map of the NTF2-like superfamily.

Eberhardt RY, Chang Y, Bateman A, Murzin AG, Axelrod HL, Hwang WC, Aravind L - BMC Bioinformatics (2013)

Bottom Line: These domains serve a range of different functions within the proteins in which they are found, including both catalytic and non-catalytic versions.Clues to the function of protein domains belonging to such a diverse superfamily can be gleaned from analysis of the proteins and organisms in which they are found.This may regulate the activities of domains with which they are combined in the same polypeptide or via operonic linkages, such as signaling domains (e.g. serine/threonine protein kinase), peptidoglycan-processing hydrolases (e.g. NlpC/P60 peptidases) or nucleic acid binding domains (e.g. Zn-ribbons).

View Article: PubMed Central - HTML - PubMed

Affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK. re3@sanger.ac.uk.

ABSTRACT

Background: The NTF2-like superfamily is a versatile group of protein domains sharing a common fold. The sequences of these domains are very diverse and they share no common sequence motif. These domains serve a range of different functions within the proteins in which they are found, including both catalytic and non-catalytic versions. Clues to the function of protein domains belonging to such a diverse superfamily can be gleaned from analysis of the proteins and organisms in which they are found.

Results: Here we describe three protein domains of unknown function found mainly in bacteria: DUF3828, DUF3887 and DUF4878. Structures of representatives of each of these domains: BT_3511 from Bacteroides thetaiotaomicron (strain VPI-5482) [PDB:3KZT], Cj0202c from Campylobacter jejuni subsp. jejuni serotype O:2 (strain NCTC 11168) [PDB:3K7C], rumgna_01855) and RUMGNA_01855 from Ruminococcus gnavus (strain ATCC 29149) [PDB:4HYZ] have been solved by X-ray crystallography. All three domains are similar in structure and all belong to the NTF2-like superfamily. Although the function of these domains remains unknown at present, our analysis enables us to present a hypothesis concerning their role.

Conclusions: Our analysis of these three protein domains suggests a potential non-catalytic ligand-binding role. This may regulate the activities of domains with which they are combined in the same polypeptide or via operonic linkages, such as signaling domains (e.g. serine/threonine protein kinase), peptidoglycan-processing hydrolases (e.g. NlpC/P60 peptidases) or nucleic acid binding domains (e.g. Zn-ribbons).

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Structures of representatives of DUF3828, DUF3887, and DUF4878. [PDB:4HYZ] is a member of DUF3887, [PDB:3K7C] is a member of DUF4878 and [PDB:3KZT] is a member of DUF3828. Structures were aligned with POSA [22] and hydrophobic surface plots generated in Chimera [23].
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Figure 6: Structures of representatives of DUF3828, DUF3887, and DUF4878. [PDB:4HYZ] is a member of DUF3887, [PDB:3K7C] is a member of DUF4878 and [PDB:3KZT] is a member of DUF3828. Structures were aligned with POSA [22] and hydrophobic surface plots generated in Chimera [23].

Mentions: The three structures ([PDB:3K7C], [PDB:3KZT] and [PDB:4HYZ]) all possess NTF2-like folds, despite being dissimilar in sequence (Figures 6 and 7, Table 1). A hydrophobic cavity with the potential for ligand-binding has been described in NTF2-like proteins before [20]. We used the MarkUs functional annotation server to locate potential cavities within the three structures [21]. All three structures contain predicted cavities, but the position of these cavities is not conserved between the structures. The structure of [PDB:3K7C] differs from that of [PDB:3KZT] and [PDB:4HYZ] in that it lacks the edge strands in the beta-sheet but has a longer helix on the opposite side. It has a shallow cavity with positive electrostatic potential that contains a bound PEG molecule in the crystal structure. Notably, in dimers seen in the crystal structure of [PDB:3K7C] the cavities of individual subunits combine in a contiguous groove that can accommodate a larger ligand than a conventional NTF-like fold can. [PDB:4HYZ] has a cavity of a similar size in a similar position with weakly positive electrostatic potential. Sequence conservation in the region of the cavities in [PDB:3K7C] and in [PDB:4HYZ] is poor. In contrast, the cavity found in [PDB:3KZT] has a negative electrostatic potential, this cavity includes two highly conserved aspartic acid residues (D-103 and D-110) which may be of significance.


Filling out the structural map of the NTF2-like superfamily.

Eberhardt RY, Chang Y, Bateman A, Murzin AG, Axelrod HL, Hwang WC, Aravind L - BMC Bioinformatics (2013)

Structures of representatives of DUF3828, DUF3887, and DUF4878. [PDB:4HYZ] is a member of DUF3887, [PDB:3K7C] is a member of DUF4878 and [PDB:3KZT] is a member of DUF3828. Structures were aligned with POSA [22] and hydrophobic surface plots generated in Chimera [23].
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3924330&req=5

Figure 6: Structures of representatives of DUF3828, DUF3887, and DUF4878. [PDB:4HYZ] is a member of DUF3887, [PDB:3K7C] is a member of DUF4878 and [PDB:3KZT] is a member of DUF3828. Structures were aligned with POSA [22] and hydrophobic surface plots generated in Chimera [23].
Mentions: The three structures ([PDB:3K7C], [PDB:3KZT] and [PDB:4HYZ]) all possess NTF2-like folds, despite being dissimilar in sequence (Figures 6 and 7, Table 1). A hydrophobic cavity with the potential for ligand-binding has been described in NTF2-like proteins before [20]. We used the MarkUs functional annotation server to locate potential cavities within the three structures [21]. All three structures contain predicted cavities, but the position of these cavities is not conserved between the structures. The structure of [PDB:3K7C] differs from that of [PDB:3KZT] and [PDB:4HYZ] in that it lacks the edge strands in the beta-sheet but has a longer helix on the opposite side. It has a shallow cavity with positive electrostatic potential that contains a bound PEG molecule in the crystal structure. Notably, in dimers seen in the crystal structure of [PDB:3K7C] the cavities of individual subunits combine in a contiguous groove that can accommodate a larger ligand than a conventional NTF-like fold can. [PDB:4HYZ] has a cavity of a similar size in a similar position with weakly positive electrostatic potential. Sequence conservation in the region of the cavities in [PDB:3K7C] and in [PDB:4HYZ] is poor. In contrast, the cavity found in [PDB:3KZT] has a negative electrostatic potential, this cavity includes two highly conserved aspartic acid residues (D-103 and D-110) which may be of significance.

Bottom Line: These domains serve a range of different functions within the proteins in which they are found, including both catalytic and non-catalytic versions.Clues to the function of protein domains belonging to such a diverse superfamily can be gleaned from analysis of the proteins and organisms in which they are found.This may regulate the activities of domains with which they are combined in the same polypeptide or via operonic linkages, such as signaling domains (e.g. serine/threonine protein kinase), peptidoglycan-processing hydrolases (e.g. NlpC/P60 peptidases) or nucleic acid binding domains (e.g. Zn-ribbons).

View Article: PubMed Central - HTML - PubMed

Affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK. re3@sanger.ac.uk.

ABSTRACT

Background: The NTF2-like superfamily is a versatile group of protein domains sharing a common fold. The sequences of these domains are very diverse and they share no common sequence motif. These domains serve a range of different functions within the proteins in which they are found, including both catalytic and non-catalytic versions. Clues to the function of protein domains belonging to such a diverse superfamily can be gleaned from analysis of the proteins and organisms in which they are found.

Results: Here we describe three protein domains of unknown function found mainly in bacteria: DUF3828, DUF3887 and DUF4878. Structures of representatives of each of these domains: BT_3511 from Bacteroides thetaiotaomicron (strain VPI-5482) [PDB:3KZT], Cj0202c from Campylobacter jejuni subsp. jejuni serotype O:2 (strain NCTC 11168) [PDB:3K7C], rumgna_01855) and RUMGNA_01855 from Ruminococcus gnavus (strain ATCC 29149) [PDB:4HYZ] have been solved by X-ray crystallography. All three domains are similar in structure and all belong to the NTF2-like superfamily. Although the function of these domains remains unknown at present, our analysis enables us to present a hypothesis concerning their role.

Conclusions: Our analysis of these three protein domains suggests a potential non-catalytic ligand-binding role. This may regulate the activities of domains with which they are combined in the same polypeptide or via operonic linkages, such as signaling domains (e.g. serine/threonine protein kinase), peptidoglycan-processing hydrolases (e.g. NlpC/P60 peptidases) or nucleic acid binding domains (e.g. Zn-ribbons).

Show MeSH
Related in: MedlinePlus