HSP47: Figures

 

Crystal structure of Hsp47 (Serpin H1)

Figure 1.Crystal structure of Hsp47 (Serpin H1). The cartoon represents the unbound (apo-) form of canine Hsp47 (PDB 4au424.

 

 

Overall structure of the Hsp47/procollagen complex

Figure 2.Overall structure of the Hsp47/procollagen complex. The cartoon shows two Hsp47 (Serpin H1) molecules complexed to three copies of procollagen a1-helix model peptides (PDB 4au3) 24.

 

 

Crystal structure of a Serpin A1 (1-antitrypsin) trimer

Figure 3.Crystal structure of a Serpin A1 (1-antitrypsin) trimer. The diagram features three copies of Serpin A1 in assembly (PDB 3t1p) 142.

 

 

The three main pathways of the mammalian Golgi stress response

Figure 4.The three main pathways of the mammalian Golgi stress response. The three main pathways of the mammalian Golgi stress response. Secretory and membrane proteins are subjected to post-translational modifications in the Golgi. When the synthesis rate of  these proteins overcomes the Golgi’s capacity, post-translational modifications occur improperly. In order to compensate for this handicap, cells will enhance the expression of modifying enzymes. Certain detectors subsequently induce down-stream transcription factors, culminating in the transcriptional activation of Golgi-related genes. Image was reproduced, with permission, from Taniguchi et al. (2017) 158.

 

 

Putative mechanism for Golgi stress-induced cell death

Figure 5. Putative mechanism for Golgi stress-induced cell death. Golgi stress improves Hsp47 expression in the ER and blocks caspase-2 cleavage in the Golgi thus preventing apoptosis-induced cell death. Hsp47-knockdown leads to enhanced cleavage of caspase-2 in the Golgi. HSP47-knockdown together with Golgi stress activates unfolded protein response (UPR)-related molecules in the ER, accompanied by activation of mitochondrial caspase-9 and cytochrome-c efflux from the mitochondria to the cytosol which leads to cell death. Image was reproduced, with permission, from Miyata et al. (2013) 4

 

 

Cartoon illustrating procollagen folding in the rough ER

Figure 6. Cartoon illustrating procollagen folding in the rough ER. Newly synthesized preprocollagen is inserted co-translationally into the ER. Cleavage of the presequence yields the pro-alpha chains that associate at the C-propeptide region followed by a zipper-like triple-helix formation from the C- to the N-terminus. Hsp47 binds to triple-helical procollagen in the ER and dissociates in the cis-Golgi or ERGIC under low pH. Triple-helical procollagen is shipped subsequently to the Golgi, packed and secreted via exocytosis. After cleavage of the C- and N-propeptides yielding tropocolloagen, collagen fibrils and fibers are generated. For details see text.