InterPro domain: IPR011057

This superfamily represents a structural domain with a complex fold consisting of several coiled beta-sheets. This domain exists as a duplication, consisting of a tandem repeat of two similar structural motifs. These domains can be found in:

• Mss4, which contains a zinc-binding site.
• Translationally controlled tumour-associated protein TCTP, which contains an insertion of an alpha-helix hairpin, and which lacks a zinc-binding site.
• The C-terminal MsrB domain of peptide methionine sulphoxide reductase.

Mss4 is a conserved accessory factor for Rab GTPases, which function as ubiquitous regulators of intracellular membrane trafficking [ 1 ]. Mss4 acts to promote nucleotide release from exocytic but not endocytic Rab GTPases. Mss4 has a complex fold made of several coiled beta-sheets, and consists of a duplication of tandem repeats of two similar structural motifs. It contains a zinc-binding site.

Other proteins that show structure similarity to Mss4 include the translationally controlled tumour-associated proteins TCTPs, which contains an insertion of an alpha helical hairpin, and lacks the zinc-binding site. TCTPs are a highly conserved and abundantly expressed family of eukaryotic proteins that are implicated in both cell growth and the human acute allergic response [ 2 ].

The C-terminal MsrB domain of peptide methionine sulphoxide reductase PilB is structurally similar to Mss4. Methionine sulphoxide reductases protect against oxidative damage that can contribute to cell death. The tandem Msr domains (MsrA and MsrB) of the pilB protein from Neisseria gonorrhoeae each reduce different epimeric forms of methionine sulphoxide [ 3 ].

1. A helical turn motif in Mss4 is a critical determinant of Rab binding and nucleotide release. Biochemistry 40, 3027-36
2. Structure of TCTP reveals unexpected relationship with guanine nucleotide-free chaperones. Nat. Struct. Biol. 8, 701-4
3. The mirrored methionine sulfoxide reductases of Neisseria gonorrhoeae pilB. Nat. Struct. Biol. 9, 348-52