Three-dimensional structure of heat shock protein 90 from Plasmodium falciparum: molecular modelling approach to rational drug design against malaria

2007 ◽  
Vol 32 (3) ◽  
pp. 531-536 ◽  
Author(s):  
Ranjit Kumar ◽  
Soundara Raghavan Pavithra ◽  
Utpal Tatu
Keyword(s):  
Plasmodium Falciparum ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Molecular Modelling ◽  
Three Dimensional ◽  
Heat Shock Protein 90 ◽  
Rational Drug Design ◽  
Dimensional Structure ◽  
Rational Drug ◽  
Modelling Approach

scholarly journals Heat Shock Protein Genes Undergo Dynamic Alteration in Their Three-Dimensional Structure and Genome Organization in Response to Thermal Stress

2017 ◽  
Vol 37 (24) ◽  
Author(s):  
Surabhi Chowdhary ◽  
Amoldeep S. Kainth ◽  
David S. Gross
Keyword(s):  
Thermal Stress ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Rna Polymerase Ii ◽  
De Novo ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Chromosome Conformation ◽  
Coding Regions ◽  
Response To Stress

ABSTRACT Three-dimensional (3D) chromatin organization is important for proper gene regulation, yet how the genome is remodeled in response to stress is largely unknown. Here, we use a highly sensitive version of chromosome conformation capture in combination with fluorescence microscopy to investigate Heat Shock Protein (HSP) gene conformation and 3D nuclear organization in budding yeast. In response to acute thermal stress, HSP genes undergo intense intragenic folding interactions that go well beyond 5′-3′ gene looping previously described for RNA polymerase II genes. These interactions include looping between upstream activation sequence (UAS) and promoter elements, promoter and terminator regions, and regulatory and coding regions (gene “crumpling”). They are also dynamic, being prominent within 60 s, peaking within 2.5 min, and attenuating within 30 min, and correlate with HSP gene transcriptional activity. With similarly striking kinetics, activated HSP genes, both chromosomally linked and unlinked, coalesce into discrete intranuclear foci. Constitutively transcribed genes also loop and crumple yet fail to coalesce. Notably, a missense mutation in transcription factor TFIIB suppresses gene looping, yet neither crumpling nor HSP gene coalescence is affected. An inactivating promoter mutation, in contrast, obviates all three. Our results provide evidence for widespread, transcription-associated gene crumpling and demonstrate the de novo assembly and disassembly of HSP gene foci.

First model of dimeric LRRK2: the challenge of unrevealing the structure of a multidomain Parkinson's-associated protein

2016 ◽  
Vol 44 (6) ◽  
pp. 1635-1641 ◽  
Author(s):  
Giambattista Guaitoli ◽  
Bernd K. Gilsbach ◽  
Francesco Raimondi ◽  
Christian Johannes Gloeckner
Keyword(s):  
Kinase Activity ◽  
Structural Model ◽  
Three Dimensional ◽  
Kinase Domain ◽  
Rational Drug Design ◽  
Dimensional Structure ◽  
Rational Drug ◽  
Its Gene ◽  
Lrrk2 Gene ◽  
Successful Approach

Mutations within the leucine-rich repeat kinase 2 (LRRK2) gene represent the most common cause of Mendelian forms of Parkinson's disease, among autosomal dominant cases. Its gene product, LRRK2, is a large multidomain protein that belongs to the Roco protein family exhibiting GTPase and kinase activity, with the latter activity increased by pathogenic mutations. To allow rational drug design against LRRK2 and to understand the cross-regulation of the G- and the kinase domain at a molecular level, it is key to solve the three-dimensional structure of the protein. We review here our recent successful approach to build the first structural model of dimeric LRRK2 by an integrative modeling approach.

Sign in / Sign up

Export Citation Format

Share Document