Journal article
Propeptides of eukaryotic proteases encode histidines to exploit organelle pH for regulation
The FASEB journal, Vol.27(8), pp.2939-2945
08/2013
Handle:
https://hdl.handle.net/2376/110950
PMCID: PMC3714588
PMID: 23585398
Abstract
Eukaryotic cells maintain strict control over protein secretion, in part by using the pH gradient maintained within their secretory pathway. How eukaryotic proteins evolved from prokaryotic orthologs to exploit the pH gradient for biological functions remains a fundamental question in cell biology. Our laboratory previously demonstrated that protein domains located within precursor proteins, propeptides, encode histidine‐driven pH sensors to regulate organelle‐specific activation of the eukaryotic proteases furin and proprotein convertase‐1/3. Similar findings have been reported in other unrelated protease families. By analyzing >10,000 unique proteases within evolutionarily unrelated families, we show that eukaryotic propeptides are enriched in histidines compared with prokaryotic orthologs. On this basis, we hypothesize that eukaryotic proteins evolved to enrich histidines within their propeptides to exploit the tightly controlled pH gradient of the secretory pathway, thereby regulating activation within specific organelles. Enrichment of histidines in propeptides may therefore be used to predict the presence of pH sensors in other proteases or even protease substrates.—Elferich, J., Williamson, D. M., Krishnamoorthy, B., Shinde, U., Propeptides of eukaryotic proteases encode histidines to exploit organelle pH for regulation. FASEB J. 27, 2939–2945 (2013). www.fasebj.org
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Details
- Title
- Propeptides of eukaryotic proteases encode histidines to exploit organelle pH for regulation
- Creators
- Johannes Elferich - Oregon Health and Science UniversityDanielle M Williamson - Oregon Health and Science UniversityBala Krishnamoorthy - Washington State UniversityUjwal Shinde - Oregon Health and Science University
- Publication Details
- The FASEB journal, Vol.27(8), pp.2939-2945
- Publisher
- Federation of American Societies for Experimental Biology; Bethesda, MD, USA
- Number of pages
- 7
- Grant note
- American Heart Association (12PRE11470005) American Heart Foundation U.S. National Institutes of Health U.S. National Science Foundation (MCB0746589)
- Identifiers
- 99900547296601842
- Language
- English
- Resource Type
- Journal article