MAMMALIAN AMYLOID HAS USEFUL ROLE - C&EN Global

Dec 5, 2005 - AMYLOID, AN INSOLUBLE AND fibrous protein aggregate, is usually thought of as a bad actor. It's associated with disorders like Alzheimer...
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NEWS OF THE WEEK PROTEIN

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FOLDING

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Tyrosinase

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MAMMALIAN AMYLOID HAS USEFUL ROLE

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Fibers that have amyloid structure serve as templates for melanin biosynthesis

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MYLOID, AN INSOLUBLE AND

fibrous protein aggregate, is usually thought of as a bad actor. It's associated with disorders like Alzheimer's disease and type 2 diabetes, so preventing its formation is considered highly desirable. Now, however, researchers at Scripps Re­ search Institute find for the first time that amyloid also plays a useful or even essential role in mammals (PLoSBw/.2006,4,c6). In mammalian cell experi­ ments, chemistry professorJeffery W. Kelly, cell biology professor William E. Balch, and cowork­ ers have found that the protein Pmell7 adopts an amyloid fold in cell organelles called melanosomes and provides a template that ap­ proximately doubles the rate of polymerization of melanin, a biopolymer that protects cells against U V and oxidative damage. The amyloid also binds and possibly mitigates the toxicity of reactive compounds in melanosomes. The Scripps work elucidates the mecha­ nism of melanin biosynthesis and could also lead to a better under­ standing of amyloid pathology and to the discovery of other function­ al, npnpathologic amyloid. Amyloid with normal function has been found in bacteria and yeast and in spider silk but never in mammals. Amyloid generally forms insoluble "plaques" that can be highly toxic to mammalian cells. "So the finding that amyloid can be beneficial in higher organ­ isms is a significant step forward in understanding the nature of this alternative form of protein struc­ ture," comments Christopher M. Dobson, professor of chemical and structural biology at Cambridge University, in England. WWW.CEN-0NLINE.ORG

Kelly, Balch, and coworkers propose the name "amyloidin" for functional amyloid, "with the ex­ pectation that the number and di­ versity of structures of this type will continue to grow," they write. "This paper adds a new dimen­ sion to the increasing evidence that the amyloid structure is a ge­ neric form of protein structure," says Dobson, whose group has demonstrated that many ordinary proteins, not just those present in disease states, are capable of form­ ing amyloidfibrils.The new study "should fuel still further the search for more examples ofthe functional use of the amyloid structure." Robert Tycko of the National Institute of Diabetes & Digestive & Kidney Diseases, Bethesda, Md., a specialist in amyloid struc­ ture, says the work is "quite inter-

INDUSTRIAL

Tyrosine

lndole-5,6quinone

Melanin PmeM 7 amyloid

TEMPLATE In melanosomes (oval), tyrosinase catalyzes the transformation of substrates like tyrosine into activated melanin precursors such as indole-5,6-quinone (red spheres). The precursors are oriented by amyloid fibrils for polymerization into melanin.

esting" and comments that it 'Svill undoubtedly stimulate future ef­ forts to find additional functional amyloids, elucidate their mecha­ nisms, and possibly develop new uses for amyloid fibrils based on their biological roles." There are caveats, however. A researcher in the field who re­ quests anonymity comments that the paper's experimental evidence for amyloid-templated biosynthesis "is weak. The rate acceleration pro­ vided by thefibrilsis only 2.2-fold, and if the mechanism invoked by the authors was operating, I would expect at least an order of magni­ tude greater acceleration."—STU BORMAN

SECURITY

New Jersey Mandates Chemical Plant Security

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n Nov. 29, Acting Gov. Richard J. Codey an­ nounced an order making New Jersey the first state in the nation to have mandatory standards for chemical plant security. There are no equivalent national standards. The states UO chemical facilities now are ex­ plicitly required to implement existing best se­ curity practices guidelines. These were large­ ly crafted by the chemical industry and roughly based on the American Chemistry Council's Re­ sponsible Care security code. They were ap­ proved in 2003 by New Jersey's Domestic Se­ curity Preparedness Task Force to protect communities against catastrophic chemical re­ leases caused by terrorist attacks. The standards continue the site-specific secu­ rity assessments of the best practices. Although the 72 member companies of the Chemistry Council of New Jersey (CCN J) have implemented

this requirement, all UO chemical facilities now must evaluate potential vulnerabilities and likely consequences of a chemical release. All UO facilities also must prepare an incident prevention and response plan and track the imple­ mentation of other best security practices. New to the standards is a requirement that workers take part in the development of the security assess­ ments and the prevention and response plans. As part of the new requirements, 43 of the UO fa­ cilities are subject to the state's Toxic Catastrophe Prevention Act and therefore must assess the po­ tential for adopting inherently safer technology, in­ cluding the substitution of less hazardous materi­ als. Industry has opposed this provision, and a CCN J statement says, "The prescriptive order [adds] re­ quirements that have little to do with security." Facilities have 120 days to develop vulnerability assessments.—LOIS EMBER

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