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Metamorphic Protein Could Lead to New AIDS-Fighting Drugs

Jan. 2, 2014

The Medical College of Wisconsin (MCW) has received a one-year, $353,000 grant from the National Institutes of Health’s National Institute of Allergy and Infectious Diseases (NIAID) to study a unique protein that shows promise as an HIV inhibitor.

Brian Volkman, PhD, professor of biochemistry at MCW, is the primary investigator of the grant.

The United Nations estimates that more than 35 million people worldwide are living with HIV, the virus which causes AIDS. There is no cure for HIV, but a variety of medications can be used to control the virus. In this project, Dr. Volkman’s team will investigate the characteristics of ‘metamorphic’ proteins, a newly discovered class of proteins which are unlike typical proteins in that they transform between two specific folded arrangements. Lymphotactin, a prototypical metamorphic protein, was recently shown to bind HIV particles and to inhibit infection of T cells. In a study published in PLoS Pathogens, http://dx.plos.org/10.1371/journal.ppat.1003852, Paolo Lusso, PhD, a scientist at NIAID, and his team at compared the antiviral activity of various lymphotactin proteins designed and produced Dr. Volkman’s lab.

Christina Guzzo, PhD, is lead author of the paper. Other co-authors at NAIAD include Yin Lin, PhD; Huiyi Miao, PhD; Raffaello Cimbro, PhD; and Anthony Fauci, PhD. MCW contributors are Dr. Volkman and Jamie Fox, PhD. The study was supported by NIH grant R01AI063325.

Because an engineered version of lymphotactin that is locked into one of the two folded arrangements lost the ability to bind or inhibit HIV, the ability to transform appears to be necessary for its biological function. The new project, supported by NIH grant R56AI103225, will fund experiments in Dr. Volkman’s lab to determine whether the metamorphic behavior of lymphotactin is important for inhibition of HIV or other human pathogens.

Once its antiviral activity is understood in the context of the metamorphic structure, lymphotactin may be developed as the lead compound in a new class of HIV-1 inhibitors with the potential to reduce the health burden of HIV/AIDS.

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