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A synthesis of research on keystone species is nonetheless missing a critical component \u2013 the sensory mechanisms for behavioral interactions that determine population\u2010 and community\u2010wide attributes. Here, we establish the chemosensory basis for keystone predation by sea stars (<jats:italic>Pisaster ochraceus<\/jats:italic>) on mussels. This consumer\u2010resource interaction is prototypic of top\u2010down driven trophic cascades. Each mussel species (<jats:italic>Mytilus californianus<\/jats:italic> and <jats:italic>M.\u00a0galloprovincialis<\/jats:italic>) secretes a glycoprotein orthologue (29.6 and 28.1\u00a0kDa, respectively) that acts, singularly, to evoke the sea star predatory response. The orthologues (named \u201c<jats:styled-content style=\"fixed-case\">KEYSTONE<\/jats:styled-content>in\u201d) are localized in the epidermis, extrapallial fluid, and organic shell coating (periostracum) of live, intact mussels. Thus, <jats:styled-content style=\"fixed-case\">KEYSTONE<\/jats:styled-content>in contacts chemosensory receptors on tube feet as sea stars crawl over rocky surfaces in search of prey. The complete nucleotide sequences reveal that <jats:styled-content style=\"fixed-case\">KEYSTONE<\/jats:styled-content>in shares 87% (<jats:italic>M.\u00a0californianus<\/jats:italic>) or 98% (<jats:italic>M.\u00a0galloprovincialis<\/jats:italic>) homology with a calcium\u2010binding protein in the shell matrix of a closely related congener, <jats:italic>M.\u00a0edulis<\/jats:italic>. All three molecules cluster tightly within the Complement Component 1 Domain Containing (C1q<jats:styled-content style=\"fixed-case\">DC<\/jats:styled-content>) protein family; each exhibits a large globular domain, low complexity region(s), coiled coil, and at least four of five histidine\u2010aspartic acid tandem motifs. Collective results support the hypothesis that <jats:styled-content style=\"fixed-case\">KEYSTONE<\/jats:styled-content>in evolved ancestrally in immunological, and later, in biomineralization roles. More recently, the substance has become exploited by sea stars as a contact cue for prey recognition. As the first identified compound to evoke keystone predation, <jats:styled-content style=\"fixed-case\">KEYSTONE<\/jats:styled-content>in provides valuable sensory information, promotes biodiversity, and shapes community structure and function. Without this molecule, there would be no predation by sea stars on mussels.<\/jats:p>","DOI":"10.1002\/ecy.1849","type":"journal-article","created":{"date-parts":[[2017,4,5]],"date-time":"2017-04-05T17:23:37Z","timestamp":1491413017000},"page":"1710-1721","source":"Crossref","is-referenced-by-count":20,"title":["Keystone predation and molecules of keystone significance"],"prefix":"10.1002","volume":"98","author":[{"given":"Richard K.","family":"Zimmer","sequence":"first","affiliation":[{"name":"Department of Ecology and Evolutionary Biology University of California Los Angeles California 90095 USA"},{"name":"Moreton Bay Research Station Centre for Marine Science School of Biological Sciences University of Queensland Brisbane Queensland 4072 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graham A.","family":"Ferrier","sequence":"additional","affiliation":[{"name":"Department of Ecology and Evolutionary Biology University of California Los Angeles California 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