InterPro domain: IPR011323

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. This entry represents copies of this structural motif in the following protein families:

• 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.

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 structural similarity to Mss4 include the translationally controlled tumour-associated proteins TCTPs, which contain an insertion of an alpha helical hairpin, and lack 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 ].

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