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2001-2004 Publications

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The inhibitor of apoptosis proteins (IAPs) represent the only endogenous cascade inhibitors and are characterized by the presence of baculoviral IAP repeats (BIRs). Here, we report the crystal structure of the complex between human caspase-7 and XIAP (BIR2 and the proceeding linker). The structure surprisingly reveals that the linker is the only contacting element for the caspase, while the  Read More

Highlights
* = co-first author, † = corresponding author
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ABAD Directly Links Aβ to Mitochondrial Toxicity in Alzheimer’s Disease

Lustbader J*, Cirilli M*, Lin C*, Xu H W, Caspersen C, Wang N, Takuma K, Chen X, Chaney M, Trinchese F, Liu S,
Kuppusamy P, Zewier Z, Arancio O, Stern D, Yan S D*†, Wu H*†. Science (2004). PDF

Mitochondrial dysfunction is a hallmark of β-amyloid (Aβ)–induced neuronal toxicity in Alzheimer’s disease (AD). Here, we demonstrate that Aβ-binding alcohol dehydrogenase (ABAD) is a direct molecular link from Aβ to mitochondrial toxicity. Aβ interacts with ABAD in the mitochondria of AD patients and transgenic mice. The crystal structure of Aβ-bound ABAD shows substantial deformation of the active site that... Read More

DNA binding is required for the apoptogenic action of apoptosis inducing factor

Ye H, Cande C, Stephanou N, Gurgusani S, Larochette N, Daugas E, Garrido C, Kroemer G, Wu H†. Nature Structural Biology (2002). PDF 

The execution of apoptosis or programmed cell death comprises both caspase-dependent and caspase-independent processes. Apoptosis inducing factor (AIF) was identified as a major player in caspase-independent cell death. It induces chromatin condensation and initial DNA cleavage via an unknown molecular mechanism. Here we report the crystal structure of human AIF at 1.8 Å resolution... Read More

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Distinct molecular mechanism for initiating TRAF6 signalling

Ye H*, Arron J*, Lamothe B, Cirilli M, Kobayashi T, Shvede N, Segal D, Dzivenu O, Vologodskaia M*, Yim M, Du K, Singh S, Pike J W, Darnay B, Choi Y, Wu H†. Nature (2002). PDF 

Tumour-necrosis factor (TNF) receptor-associated factor 6 (TRAF6) is the only TRAF family member that participates in signal transduction of both the TNF receptor (TNFR) superfamily and the interleukin-1 receptor (IL-1R)/Toll-like receptor (TLR) superfamily1–5; it is important for adaptive immunity, innate immunity and bone homeostasis. Here we report crystal structures of TRAF6, alone and in complex with... Read More

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Structural Basis of Caspase Inhibition by XIAP: Differential Roles of the Linker versus the BIR Domain

Huang Y*, Park Y C*, Rich R L, Segal D, Myszka D G, Wu H†. Cell (2001). PDF 

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Covalent inhibition revealed by the crystal structure of the caspase-8/p35 complex

Xu G, Cirilli M, Huang Y, Rich R L, Myszka D G, Wu H†. Nature (2001). PDF

Apoptosis is a highly regulated process that is crucial for normal development and homeostasis of multicellular organisms. The p35 protein from baculoviruses effectively prevents apoptosis by its broad-spectrum caspase inhibition. Here we report the crystal structure of p35 in complex with human caspase-8 at 3.0 Å resolution and biochemical and mutagenesis studies based on the structural information... Read More

Other Publications (2001-2004)
* = co-first author, † = corresponding author
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Huang Y, Lu M, Wu H†. (2004). XIAP inhibitors for cancer treatment: removing the brakes of apoptosis? Cancer Cell. 5:1-2

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Ye H, Chen T, Xu X, Pennycooke M, Wu H† , Steegborn C† . (2004). Crystal structure of the putative adapter protein MTH1859. J Struct Biol. 148:251-6

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Dzivenu O K, Park H H, Wu H†. (2004). General co-expression vectors for the overexpression of heterodimeric protein complexes in Escherichia coli. Protein Expr Purif. 38: 1-8

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Huang Y, Lu M, Wu H†. (2004). Antagonizing XIAP-mediated caspase-3 inhibition. Achilles' heel of cancers? Cancer Cell. 5:1-2

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Wu H*. (2004). Assembly of post-receptor signaling complexes for the TNF receptor superfamily. Advances in Protein Chemistry. 68:225-79

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Park H H, Wu H†. (2004). Gauging length: recognition of small interfering RNAs. Structure. 12:172-173

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Moldovan MC*, Yachou A*, Levesque K, Wu H, Hendrickson WA, Cohen EA, Sekaly RP†. (2002). CD4 dimers constitute the functional component required for T cell activation. J. Immunology. 169:6261-8

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Xu G, Rich R L, Steegborn C, Min T, Huang Y, Myszka D G, Wu H†. (2003). Mutational Analyses of the p35/caspase Interaction: A bowstring kinetic model of caspase inhibition by P35. J Biol Chem. 278:5455-61

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Huang Y, Rich R, Myszka D, Wu H†. (2003). Requirement of both the BIR2 and BIR3 domains for the relief of XIAP-mediated caspase inhibition by Smac. J Biol Chem. 278:49517-22

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Chung J, Park Y C, Ye H, Wu H. (2003). TNF receptor associated factors. In Handbook of Cell Signaling. 1:311

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Wu H†, Arron J. (2003). TRAF6, a molecular bridge of adaptive immunity, innate immunity and bone homeostasis. Bioessays. 25:1096-1105

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Ye H, Cirilli M, Wu H†. (2002). The use of construct variation and diffraction data analysis in the crystallization of the TRAF domain of human tumor necrosis factor receptor associated factor 6. Acta Crystallogr D Biol Crystallogr. 58:1886-1888

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Chung J, Park Y C, Ye H, Wu H†. (2002). All TRAFs are not created equal: common and distinct molecular mechanisms of TRAF-mediated signal transduction. J Cell Sci. 115:679-688

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