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Solution structure of Mcl‐1 and its complexes
Author(s) -
Hinds Mark G.,
Day Catherine L.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a638-b
Subject(s) - bcl 2 family , apoptosis , chemistry , programmed cell death , biology , microbiology and biotechnology , biochemistry
Bcl‐2 family proteins integrate many signaling pathways leading to cell death (apoptosis). Pro‐survival members of this family, such as Mcl‐1, are aberrantly regulated in many cancers. Pro‐survival Bcl‐2 proteins, including Mcl‐1, have a conserved helical fold while the cell killing pro‐apoptotic ‘BH3‐only’ members may have a less well‐ordered structure. We have characterized the structure of Mcl‐1 complexed with its pro‐apoptotic ‘BH3‐only’ partners. As with other pro‐survival proteins, the BH3‐ligand lies in the groove of Mcl‐1 becoming a well‐ordered helix on binding. Our structural analysis indicates the intermolecular interactions in the complexes are a combination of conserved contacts shared with other pro‐survival Bcl‐2 proteins and unique interactions that confer the distinctive binding profile upon Mcl‐1. Analysis of these structures may provide a structural basis for antagonist design. Supported by the Marsden Fund (NZ), Leukemia and Lymphoma Society, and NHMRC (Aus). Poster presented at Keystone Symposia, Frontiers of NMR and Molecular Biology, Banff, 29 January ‐ 4 February, 2005; (presented Monday, January 31, 2005)