A common fold mediates vertebrate defense and bacterial attack

Carlos Joaquim Rosado, Ashley Maurice Buckle, Ruby Hong Ping Law, Rebecca Elizabeth Butcher, Wan-Ting Kan, Catherina Hedwig Bird, Kheng Sok Ung, Kylie A Browne, Katherine Baran, Tanya Ann Bashtannyk-Puhalovich, Noel Garry Faux, Wilson Wong, Corrine Joy Porter, Robert Neil Pike, Andrew Malcolm Ellisdon, Mary Catherine Pearce, Stephen Paul Bottomley, Jonas Emsley, Alexander Ian Smith, Jamie RossjohnElizabeth Louise Hartland, Ilia Voskoboinik, Joseph A Trapani, Phillip Ian Bird, Michelle Anne Dunstone, James Whisstock

Research output: Contribution to journalArticleResearchpeer-review

208 Citations (Scopus)

Abstract

Proteins containing Membrane Attack Complex / Perforin (MACPF) domains play important roles in vertebrate immunity, embryonic development and neural cell migration. In vertebrates, C9 and perforin form oligomeric pores that lyse bacteria and kill virus-infected cells, respectively. However, the mechanism of MACPF function is unknown. We determined the crystal structure of a bacterial MACPF protein, Plu-MACPF from Photorhabdus luminescens, to 2.0 A resolution. The MACPF domain reveals structural similarity with pore forming cholesterol-dependent cytolysins (CDCs) from Gram positive bacteria. This suggests that lytic MACPF proteins may use a CDC-like mechanism to form pores and disrupt cell membranes. Sequence similarity between bacterial and vertebrate MACPF domains suggest that the fold of the CDCs, a family of proteins important for bacterial pathogenesis, is likely used by vertebrates for defence against infection.
Original languageEnglish
Pages (from-to)1548 - 1551
Number of pages4
JournalScience
Volume317
Issue number5844
Publication statusPublished - 2007

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