Structure of TCTP reveals unexpected relationship with guanine nucleotide-free chaperones.
The translationally controlled tumor-associated proteins (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 but whose intracellular biochemical function has remained elusive. We report here the solution structure of the TCTP from Schizosaccharomyces pombe, which, on the basis of sequence homology, defines the fold of the entire family. We show that TCTPs form a structural superfamily with the Mss4/Dss4 family of proteins, which bind to the GDP/GTP free form of Rab proteins (members of the Ras superfamily) and have been termed guanine nucleotide-free chaperones (GFCs). Mss4 also acts as a relatively inefficient guanine nucleotide exchange factor (GEF). We further show that the Rab protein binding site on Mss4 coincides with the region of highest sequence conservation in the TCTP family. This is the first link to any other family of proteins that has been established for the TCTP family and suggests the presence of a GFC/GEF at extremely high abundance in eukaryotic cells.
Thaw
P
P
Krebs Institute for Biomolecular Research, Department of Molecular Biology and Biotechnology, University of Sheffield, Firth Court, Western Bank, Sheffield, S10 2TN, UK.
Baxter
N J
NJ
Hounslow
A M
AM
Price
C
C
Waltho
J P
JP
Craven
C J
CJ
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001665:Binding Sites; D014408:Biomarkers, Tumor; D017124:Conserved Sequence; D005656:Fungal Proteins / Q000737:chemistry; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000378:metabolism; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D008222:Lymphokines / Q000737:chemistry*; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D012568:Schizosaccharomyces / Q000737:chemistry*; D016415:Sequence Alignment; D000090324:Tumor Protein, Translationally-Controlled 1; D020691:rab GTP-Binding Proteins / Q000378:metabolism
D014408:Biomarkers, Tumor; D005656:Fungal Proteins; D020662:Guanine Nucleotide Exchange Factors; D008222:Lymphokines; D018832:Molecular Chaperones; D011506:Proteins; C489794:RABIF protein, human; C000715647:TPT1 protein, human; D000090324:Tumor Protein, Translationally-Controlled 1; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; D020691:rab GTP-Binding Proteins