Sequence-independent recognition of the amyloid structural motif by GFP protein family

Cnidarian fluorescent protein (FP) derivatives such as GFP, mCherry, and mEOS2 have been widely used to monitor gene expression and protein localization through biological imaging because they are considered functionally inert. We demonstrate that FPs specifically bind amyloid fibrils formed from ma...

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Published in:	Proceedings of the National Academy of Sciences - PNAS Vol. 117; no. 36; pp. 22122 - 22127
Main Authors:	Xu, Sherry C. S., LoRicco, Josephine G., Bishop, Anthony C., James, Nathan A., Huynh, Welby H., McCallum, Scott A., Roan, Nadia R., Makhatadze, George I.
Format:	Journal Article
Language:	English
Published:	United States National Academy of Sciences 08-09-2020
Subjects:	Actin Aggregates Amino Acid Sequence Amyloidogenic Proteins - chemistry Biological Sciences Diagnostic software Diagnostic systems Elongation Fibrils Filaments Fluorescence Fusion protein Gene expression Green fluorescent protein Green Fluorescent Proteins - chemistry Humans Lag phase Localization Luminescent Proteins Microscopy, Confocal - methods Microtubules Peptides Protein Conformation Proteins Red Fluorescent Protein GFP-like proteins binding inhibition amyloid fibril
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Summary:	Cnidarian fluorescent protein (FP) derivatives such as GFP, mCherry, and mEOS2 have been widely used to monitor gene expression and protein localization through biological imaging because they are considered functionally inert. We demonstrate that FPs specifically bind amyloid fibrils formed from many natural peptides and proteins. FPs do not bind other nonamyloid fibrillar structures such as microtubules or actin filaments and do not bind to amorphous aggregates. FPs can also bind small aggregates formed during the lag phase and early elongation phase of fibril formation and can inhibit amyloid fibril formation in a dose-dependent manner. These findings suggest caution should be taken in interpreting FP-fusion protein localization data when amyloid structures may be present. Given the pathological significance of amyloid-related species in some diseases, detection and inhibition of amyloid fibril formation using FPs can provide insights on developing diagnostic tools.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Author contributions: S.C.S.X., J.G.L., A.C.B., and G.I.M. designed research; S.C.S.X., J.G.L., A.C.B., N.A.J., and W.H.H. performed research; S.A.M. and N.R.R. contributed new reagents/analytic tools; S.C.S.X., J.G.L., A.C.B., N.A.J., W.H.H., S.A.M., N.R.R., and G.I.M. analyzed data; and S.C.S.X., J.G.L., A.C.B., N.A.J., W.H.H., S.A.M., N.R.R., and G.I.M. wrote the paper. Edited by Susan Marqusee, University of California, Berkeley, CA, and approved August 5, 2020 (received for review January 24, 2020) 1S.C.S.X., J.G.L., and A.C.B. contributed equally to this work.
ISSN:	0027-8424 1091-6490
DOI:	10.1073/pnas.2001457117