Human polyhomeotic homolog 3 (PHC3) sterile alpha motif (SAM) linker allows open-ended polymerization of PHC3 SAM

Angela K. Robinson, Belinda Z. Leal, David R. Nanyes, Yogeet Kaur, Udayar Ilangovan, Virgil Schirf, Andrew P. Hinck, Borries Demeler, Chongwoo A. Kim

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4 Scopus citations

Abstract

Sterile alpha motifs (SAMs) are frequently found in eukaryotic genomes. An intriguing property of many SAMs is their ability to self-associate, forming an open-ended polymer structure whose formation has been shown to be essential for the function of the protein. What remains largely unresolved is how polymerization is controlled. Previously, we had determined that the stretch of unstructured residues N-terminal to the SAM of a Drosophila protein called polyhomeotic (Ph), a member of the polycomb group (PcG) of gene silencers, plays a key role in controlling Ph SAM polymerization. Ph SAM with its native linker created shorter polymers compared to Ph SAM attached to either a random linker or no linker. Here, we show that the SAM linker for the human Ph ortholog, polyhomeotic homolog 3 (PHC3), also controls PHC3 SAM polymerization but does so in the opposite fashion. PHC3 SAM with its native linker allows longer polymers to form compared to when attached to a random linker. Attaching the PHC3 SAM linker to Ph SAM also resulted in extending Ph SAM polymerization. Moreover, in the context of full-length Ph protein, replacing the SAM linker with PHC3 SAM linker, intended to create longer polymers, resulted in greater repressive ability for the chimera compared to wild-type Ph. These findings show that polymeric SAM linkers evolved to modulate a wide dynamic range of SAM polymerization abilities and suggest that rationally manipulating the function of SAM containing proteins through controlling their SAM polymerization may be possible.

Original languageEnglish (US)
Pages (from-to)5379-5386
Number of pages8
JournalBiochemistry
Volume51
Issue number27
DOIs
StatePublished - Jul 10 2012

ASJC Scopus subject areas

  • Biochemistry

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    Robinson, A. K., Leal, B. Z., Nanyes, D. R., Kaur, Y., Ilangovan, U., Schirf, V., Hinck, A. P., Demeler, B., & Kim, C. A. (2012). Human polyhomeotic homolog 3 (PHC3) sterile alpha motif (SAM) linker allows open-ended polymerization of PHC3 SAM. Biochemistry, 51(27), 5379-5386. https://doi.org/10.1021/bi3004318