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Structural and Biological Interaction of hsc-70 Protein with Phosphatidylserine in Endosomal Microautophagy
| Content Provider | Scilit |
|---|---|
| Author | Morozova, Kateryna Clement, Cristina C. Kaushik, Susmita Stiller, Barbara Arias, Esperanza Ahmad, Atta Rauch, Jennifer N. Chatterjee, Victor Melis, Chiara Scharf, Brian Gestwicki, Jason E. Cuervo, Ana-Maria Zuiderweg, Erik R. P. Santambrogio, Laura |
| Copyright Year | 2016 |
| Description | Journal: Journal of Biological Chemistry Hsc-70 (HSPA8) is a cytosolic molecular chaperone, which plays a central role in cellular proteostasis, including quality control during protein refolding and regulation of protein degradation. hsc-70 is pivotal to the process of macroautophagy, chaperone-mediated autophagy, and endosomal microautophagy. The latter requires hsc-70 interaction with negatively charged phosphatidylserine (PS) at the endosomal limiting membrane. Herein, by combining plasmon resonance, NMR spectroscopy, and amino acid mutagenesis, we mapped the C terminus of the hsc-70 LID domain as the structural interface interacting with endosomal PS, and we estimated an hsc-70/PS equilibrium dissociation constant of 4.7 ± 0.1 μm. This interaction is specific and involves a total of 4–5 lysine residues. Plasmon resonance and NMR results were further experimentally validated by hsc-70 endosomal binding experiments and endosomal microautophagy assays. The discovery of this previously unknown contact surface for hsc-70 in this work elucidates the mechanism of hsc-70 PS/membrane interaction for cytosolic cargo internalization into endosomes. |
| Related Links | http://www.jbc.org/content/291/35/18096.full.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5000059/pdf http://www.jbc.org/article/S0021925820321748/pdf |
| Ending Page | 18106 |
| Page Count | 11 |
| Starting Page | 18096 |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| DOI | 10.1074/jbc.m116.736744 |
| Journal | Journal of Biological Chemistry |
| Issue Number | 35 |
| Volume Number | 291 |
| Language | English |
| Publisher | Elsevier BV |
| Publisher Date | 2016-08-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Journal of Biological Chemistry 70-kilodalton Heat Shock Protein (hsp70) Phosphatidylserine |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |