6AU8

1.8 angstrom crystal structure of the human Bag6-NLS & TRC35 complex

Summary for 6AU8

• Entry DOI: 10.2210/pdb6au8/pdb
• Descriptor: Golgi to ER traffic protein 4 homolog, Large proline-rich protein BAG6, GLYCEROL, ... (4 entities in total)
• Functional Keywords: trc pathway complex, chaperone
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 37117.29

Authors

Mock, J.Y.,Clemons Jr., W.M. (deposition date: 2017-08-31, release date: 2017-11-01, Last modification date: 2024-03-13)

Primary citation

Mock, J.Y.,Xu, Y.,Ye, Y.,Clemons, W.M.
Structural basis for regulation of the nucleo-cytoplasmic distribution of Bag6 by TRC35.
Proc. Natl. Acad. Sci. U.S.A., 114:11679-11684, 2017

PubMed Abstract: The metazoan protein BCL2-associated athanogene cochaperone 6 (Bag6) forms a hetero-trimeric complex with ubiquitin-like 4A and transmembrane domain recognition complex 35 (TRC35). This Bag6 complex is involved in tail-anchored protein targeting and various protein quality-control pathways in the cytosol as well as regulating transcription and histone methylation in the nucleus. Here we present a crystal structure of Bag6 and its cytoplasmic retention factor TRC35, revealing that TRC35 is remarkably conserved throughout the opisthokont lineage except at the C-terminal Bag6-binding groove, which evolved to accommodate Bag6, a unique metazoan factor. While TRC35 and its fungal homolog, guided entry of tail-anchored protein 4 (Get4), utilize a conserved hydrophobic patch to bind their respective partners, Bag6 wraps around TRC35 on the opposite face relative to the Get4-5 interface. We further demonstrate that TRC35 binding is critical not only for occluding the Bag6 nuclear localization sequence from karyopherin α to retain Bag6 in the cytosol but also for preventing TRC35 from succumbing to RNF126-mediated ubiquitylation and degradation. The results provide a mechanism for regulation of Bag6 nuclear localization and the functional integrity of the Bag6 complex in the cytosol.

PubMed: 29042515
DOI: 10.1073/pnas.1702940114

Experimental method

X-RAY DIFFRACTION (1.8 Å)