3kk7

Protein Summary

The structure of the protein encoded by Bacteroides theraiotaomicron gene BT_3439 (NP_812351.1) is the first representative of a new family (weak hit (E-value 0.91) with DUF1160). The structure reveals a MACPF N-terminal domain and an extra C-terminal domain, that could be further divided into three smaller domains. The top hit in SSM is 2qp2, a bacterial perforin-like protein, with 41% of secondary structure elements (SSE) matching. HHpred top hits are MACPF domains 2qp2 (E-value 4.7E-23) and 2rd7 (E-value 3.3E-18). All three hits are corroborated by Dali with Z-scores of 17.4, 12.9 and 12.3 for 2qp2, 2rd7 and 2qqh, respectively. The C-terminal domain (residues 389-528) does not have a significant match to known proteins.

The MACPF domain is involved in human complement activation and bacterial attack [Ref][Ref]. This structure is the second MACPF domain from bacteria (pdb 2qp2) and third MACPF structure [Ref]. MACPF domain is also present in human complement component C8 alpha chain (PDBs 2qqh, 2rd7).

MACPF domain  (Membrane Attacking Complex) is known to form pores inside membranes.

Figure 1. Structure of BT3439

In is interesting to note, that BT_3439 is strongly upregulated in all host-associated, but not in in vitro growing conditions of B. thetaiotaomicron, as shown by the expression data from Jeff Gordon's lab (http://www.ncbi.nlm.nih.gov/sites/GDSbrowser?acc=GDS1849)[Ref]. Expression is further increased in the presence of a simple sugar (versus polysaccharide) diet.

STRING (http://string.embl.de) predicts a functional association of BT_3439 with BT_3438, BT_3440 and BT_3441, all putative uncharacterized proteins. A cross-check with the expression data for these genes shows an identical expression profile for BT_3440 and BT_3441 and a similar one for BT_3438, in agreement with the hypothesis that these proteins may form a functional unit. Remote homology analysis reveals that BT_3440 shows significant homology with toxins (PF03318, FFAS score -36.0 and PF01117, FFAS score -25.1) further indicating that this functional unit acts as an invasion complex.

Ligand Summary