6au8

Structural highlights

Function

GET4_HUMAN As part of a cytosolic protein quality control complex, the BAG6/BAT3 complex, maintains misfolded and hydrophobic patches-containing proteins in a soluble state and participates to their proper delivery to the endoplasmic reticulum or alternatively can promote their sorting to the proteasome where they undergo degradation (PubMed:20676083, PubMed:21636303, PubMed:21743475, PubMed:28104892). The BAG6/BAT3 complex is involved in the post-translational delivery of tail-anchored/type II transmembrane proteins to the endoplasmic reticulum membrane. Recruited to ribosomes, it interacts with the transmembrane region of newly synthesized tail-anchored proteins and together with SGTA and ASNA1 mediates their delivery to the endoplasmic reticulum (PubMed:20676083, PubMed:28104892). Client proteins that cannot be properly delivered to the endoplasmic reticulum are ubiquitinated and sorted to the proteasome (PubMed:28104892). Similarly, the BAG6/BAT3 complex also functions as a sorting platform for proteins of the secretory pathway that are mislocalized to the cytosol either delivering them to the proteasome for degradation or to the endoplasmic reticulum (PubMed:21743475). The BAG6/BAT3 complex also plays a role in the endoplasmic reticulum-associated degradation (ERAD), a quality control mechanism that eliminates unwanted proteins of the endoplasmic reticulum through their retrotranslocation to the cytosol and their targeting to the proteasome. It maintains these retrotranslocated proteins in an unfolded yet soluble state condition in the cytosol to ensure their proper delivery to the proteasome (PubMed:21636303).^{[1] [2] [3] [4]}

See Also

• BAG family proteins 3D structures

References

1. ↑ Mariappan M, Li X, Stefanovic S, Sharma A, Mateja A, Keenan RJ, Hegde RS. A ribosome-associating factor chaperones tail-anchored membrane proteins. Nature. 2010 Aug 26;466(7310):1120-4. doi: 10.1038/nature09296. Epub 2010 Aug 1. PMID:20676083 doi:http://dx.doi.org/10.1038/nature09296
2. ↑ Wang Q, Liu Y, Soetandyo N, Baek K, Hegde R, Ye Y. A ubiquitin ligase-associated chaperone holdase maintains polypeptides in soluble states for proteasome degradation. Mol Cell. 2011 Jun 24;42(6):758-70. doi: 10.1016/j.molcel.2011.05.010. PMID:21636303 doi:http://dx.doi.org/10.1016/j.molcel.2011.05.010
3. ↑ Hessa T, Sharma A, Mariappan M, Eshleman HD, Gutierrez E, Hegde RS. Protein targeting and degradation are coupled for elimination of mislocalized proteins. Nature. 2011 Jul 10;475(7356):394-7. doi: 10.1038/nature10181. PMID:21743475 doi:http://dx.doi.org/10.1038/nature10181
4. ↑ Shao S, Rodrigo-Brenni MC, Kivlen MH, Hegde RS. Mechanistic basis for a molecular triage reaction. Science. 2017 Jan 20;355(6322):298-302. doi: 10.1126/science.aah6130. PMID:28104892 doi:http://dx.doi.org/10.1126/science.aah6130