TY - JOUR
T1 - Solution structure of the proapoptotic molecule BID
T2 - A structural basis for apoptotic agonists and antagonists
AU - McDonnell, James M.
AU - Fushman, David
AU - Milliman, Curt L.
AU - Korsmeyer, Stanley J.
AU - Cowburn, David
N1 - Funding Information:
We are grateful to Dr. Frank Löhr for some of the pulse sequences used; Dr. Jie Zheng for his help in early aspects of the project; and Dr. Sean Cahill for technical support. D. C. thanks Professor John Kuriyan for comments. This work was supported by NIH grants GM-47021 (D. C.) and CA-50239 (S. J. K.).
PY - 1999/3/5
Y1 - 1999/3/5
N2 - Members of the BCL2 family of proteins are key regulators of programmed cell death, acting either as apoptotic agonists or antagonists. Here we describe the solution structure of BID, presenting the structure of a proapoptotic BCL2 family member. An analysis of sequence/structure of BCL2 family members allows us to define a structural superfamily, which has implications for general mechanisms for regulating proapoptotic activity. It appears two criteria must be met for proapoptotic function within the BCL2 family: targeting of molecules to intracellular membranes, and exposure of the BH3 death domain. BID's activity is regulated by a Caspase 8-mediated cleavage event, exposing the BH3 domain and significantly changing the surface charge and hydrophobicity, resulting in a change of cellular localization.
AB - Members of the BCL2 family of proteins are key regulators of programmed cell death, acting either as apoptotic agonists or antagonists. Here we describe the solution structure of BID, presenting the structure of a proapoptotic BCL2 family member. An analysis of sequence/structure of BCL2 family members allows us to define a structural superfamily, which has implications for general mechanisms for regulating proapoptotic activity. It appears two criteria must be met for proapoptotic function within the BCL2 family: targeting of molecules to intracellular membranes, and exposure of the BH3 death domain. BID's activity is regulated by a Caspase 8-mediated cleavage event, exposing the BH3 domain and significantly changing the surface charge and hydrophobicity, resulting in a change of cellular localization.
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U2 - 10.1016/S0092-8674(00)80573-5
DO - 10.1016/S0092-8674(00)80573-5
M3 - Article
C2 - 10089878
AN - SCOPUS:0033525749
SN - 0092-8674
VL - 96
SP - 625
EP - 634
JO - Cell
JF - Cell
IS - 5
ER -