A brain-specific isoform of small glutamine-rich tetratricopeptide repeat-containing protein binds to Hsc70 and the cysteine string protein.
Small glutamine-rich tetratricopeptide repeat-containing protein (SGT) is a ubiquitously expressed cochaperone of heat shock cognate protein of 70 kDa (Hsc70). SGT binds to the C terminus of Hsc70, a site used by several tetratricopeptide repeat-containing binding partners to recruit Hsc70 into complexes of diverse function. We describe here an isoform of SGT with 60% amino acid sequence identity that we name betaSGT. In contrast to the previously published alphaSGT, betaSGT is almost exclusively expressed in brain. Both isoforms of SGT possess similar binding properties toward Hsc70 and cysteine string protein, a synaptic vesicle-associated J-domain-containing protein. In addition, SGTs oligomerize without preferences among isoforms. The distribution of protein binding motifs on SGTs reveals a modular structure. The N-terminal domains mediate oligomerization. Binding to Hsc70 is impaired by mutations of basic residues within the central tetratricopeptide repeat domain of betaSGT, indicating a two-carboxylate clamp as the binding mode. The tetratricopeptide repeats are also necessary for binding to the cysteine string protein. However, this binding mode is distinct from the two-carboxylate clamp that is involved in Hsc70 binding. The C-terminal regions of SGTs might constitute independent protein interaction domains. We conclude that betaSGT is likely to cooperate with alphaSGT as co-chaperone of Hsc70 in the brain. The modular structure of SGTs allows them to recruit client proteins to Hsc70 and to direct the resulting complex toward downstream proteins that take over the respective client proteins.
Tobaben
Sönke
S
Max Planck Institute for Experimental Medicine, Department of Molecular Neurobiology and Deutsche Forschungsgemeinschaft Center for Molecular Physiology of the Brain, Hermann-Rein-Strasse 3, D-37075 Göttingen, Germany.
Varoqueaux
Frederique
F
Brose
Nils
N
Stahl
Bernd
B
Meyer
Guido
G
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002352:Carrier Proteins; D003001:Cloning, Molecular; D003545:Cysteine / Q000737:chemistry*; D018076:DNA, Complementary / Q000378:metabolism; D015723:Gene Library; D005973:Glutamine / Q000737:chemistry*; D050883:HSC70 Heat-Shock Proteins; D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D017403:In Situ Hybridization; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D008957:Models, Genetic; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D016296:Mutagenesis; D017830:Octoxynol / Q000494:pharmacology; D017354:Point Mutation; D011485:Protein Binding; D014176:Protein Biosynthesis; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D020798:Two-Hybrid System Techniques
D002352:Carrier Proteins; D018076:DNA, Complementary; D050883:HSC70 Heat-Shock Proteins; D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C494371:HSPA8 protein, human; C494373:Hspa8 protein, rat; D008565:Membrane Proteins; D018832:Molecular Chaperones; D020033:Protein Isoforms; D011506:Proteins; D012333:RNA, Messenger; C114575:SGTA protein, human; C512694:Sgta protein, rat; C088460:cysteine string protein; D005973:Glutamine; D017830:Octoxynol; D003545:Cysteine