Mitochondrial ClpX activates an essential biosynthetic enzyme through partial unfolding
Name
elife-54387-v2.pdf
Description
Published version
Size
2.04 MB
Format
Adobe PDF
Checksum (MD5)
29a5c05684f44d290b57f0f229cfc7dd
Author(s)
Kardon, Julia R
Moroco, Jamie A
Engen, John R
Baker, Tania A
Date Issued
2020
Journal
eLife
Publisher
eLife Sciences Publications, Ltd
Version
Final published version
Abstract
© 2020, eLife Sciences Publications Ltd. All rights reserved. Mitochondria control the activity, quality, and lifetime of their proteins with an autonomous system of chaperones, but the signals that direct substrate-chaperone interactions and outcomes are poorly understood. We previously discovered that the mitochondrial AAA+ protein unfoldase ClpX (mtClpX) activates the initiating enzyme for heme biosynthesis, 5-aminolevulinic acid synthase (ALAS), by promoting cofactor incorporation. Here, we ask how mtClpX accomplishes this activation. Using S. cerevisiae proteins, we identified sequence and structural features within ALAS that position mtClpX and provide it with a grip for acting on ALAS. Observation of ALAS undergoing remodeling by mtClpX revealed that unfolding is limited to a region extending from the mtClpX-binding site to the active site. Unfolding along this path is required for mtClpX to gate cofactor binding to ALAS. This targeted unfolding contrasts with the global unfolding canonically executed by ClpX homologs and provides insight into how substrate-chaperone interactions direct the outcome of remodeling.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Howard Hughes Medical Institute
Terms of Use
Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.7554/ELIFE.54387
