Protein Structure, Quaternary

Publication Title: 
Autophagy

Amyotrophic lateral sclerosis (ALS) is a fatal motoneuron disease with no current effective treatment. Accumulation of abnormal protein inclusions containing SOD1, TARDBP, FUS, among other proteins, is a pathological hallmark of ALS. Autophagy is the major degradation pathway involved in the clearance of damaged organelles and protein aggregates. Although autophagy has been shown to efficiently degrade ALS-linked mutant protein in cell culture models, several studies suggest that autophagy impairment may also contribute to disease pathogenesis.

Author(s): 
Castillo, Karen
Nassif, Melissa
Valenzuela, Vicente
Rojas, Fabiola
Matus, Soledad
Mercado, Gabriela
Court, Felipe A.
van Zundert, Brigitte
Hetz, Claudio
Publication Title: 
PloS One

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the selective loss of motor neurons in the spinal cord, brain stem, and motor cortex. Mutations in superoxide dismutase (SOD1) are associated with familial ALS and lead to SOD1 protein misfolding and aggregation. Here we show that the molecular chaperone, HSJ1 (DNAJB2), mutations in which cause distal hereditary motor neuropathy, can reduce mutant SOD1 aggregation and improve motor neuron survival in mutant SOD1 models of ALS.

Author(s): 
Novoselov, Sergey S.
Mustill, Wendy J.
Gray, Anna L.
Dick, James R.
Kanuga, Naheed
Kalmar, Bernadett
Greensmith, Linda
Cheetham, Michael E.
Publication Title: 
Genes & Development

The Spt-Ada-Gcn5-acetyltransferase (SAGA) chromatin-modifying complex possesses acetyltransferase and deubiquitinase activities. Within this modular complex, Ataxin-7 anchors the deubiquitinase activity to the larger complex. Here we identified and characterized Drosophila Ataxin-7 and found that reduction of Ataxin-7 protein results in loss of components from the SAGA complex.

Author(s): 
Mohan, Ryan D.
Dialynas, George
Weake, Vikki M.
Liu, Jianqi
Martin-Brown, Skylar
Florens, Laurence
Washburn, Michael P.
Workman, Jerry L.
Abmayr, Susan M.
Publication Title: 
Protein Science: A Publication of the Protein Society

Glutathione S-transferase of the malarial parasite Plasmodium falciparum (PfGST) represents a novel class of GST isoenzymes. Since the architecture of the PfGST substrate binding site differs significantly from its human counterparts and there is only this one isoenzyme present in the parasite, PfGST is considered a highly attractive target for antimalarial drug development. Here we report the mechanistic, kinetic, and structural characterization of PfGST as well as its interaction with different ligands.

Author(s): 
Hiller, Nicole
Fritz-Wolf, Karin
Deponte, Marcel
Wende, Wolfgang
Zimmermann, Herbert
Becker, Katja
Publication Title: 
Antimicrobial Agents and Chemotherapy

Previous studies have shown an antimalarial effect of total alkaloids extracted from leaves of Guiera senegalensis from Mali in West Africa. We independently observed that the beta-carboline alkaloid harmine obtained from a natural product library screen inhibited Plasmodium falciparum heat shock protein 90 (PfHsp90) ATP-binding domain. In this study, we confirmed harmine-PfHsp90-specific affinity using surface plasmon resonance analysis (dissociation constant [K(d)] of 40 ?M).

Author(s): 
Shahinas, Dea
Macmullin, Gregory
Benedict, Christan
Crandall, Ian
Pillai, Dylan R.
Publication Title: 
Biochemistry

The purpose of the study was to determine the effects of truncation of various regions of betaB1-crystallin on its structural properties and stability of heterooligomers formed by wild-type (WT) betaB1 or its deletion mutants with WT betaA3-crystallin.

Author(s): 
Srivastava, K.
Gupta, R.
Chaves, J. M.
Srivastava, O. P.
Publication Title: 
The Journal of Biological Chemistry

The estrogen receptors, ERα and ERβ, are ligand-regulated transcription factors that control gene expression programs in target tissues. The molecular events underlying estrogen action involve minimally two steps, hormone binding to the ER ligand-binding domain followed by coactivator recruitment to the ER·ligand complex; this ligand·receptor·coactivator triple complex then alters gene expression.

Author(s): 
Jeyakumar, M.
Carlson, Kathryn E.
Gunther, Jillian R.
Katzenellenbogen, John A.
Publication Title: 
The Journal of Biological Chemistry

SIRT3 is a major mitochondrial NAD(+)-dependent protein deacetylase playing important roles in regulating mitochondrial metabolism and energy production and has been linked to the beneficial effects of exercise and caloric restriction. SIRT3 is emerging as a potential therapeutic target to treat metabolic and neurological diseases.

Author(s): 
Jin, Lei
Wei, Wentao
Jiang, Yaobin
Peng, Hao
Cai, Jianhua
Mao, Chen
Dai, Han
Choy, Wendy
Bemis, Jean E.
Jirousek, Michael R.
Milne, Jill C.
Westphal, Christoph H.
Perni, Robert B.
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