Alexander Lemak
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View article: The RavA-ViaA chaperone complex modulates bacterial persistence through its association with the fumarate reductase enzyme
The RavA-ViaA chaperone complex modulates bacterial persistence through its association with the fumarate reductase enzyme Open
Regulatory ATPase variant A (RavA) is a MoxR AAA+ protein that functions together with a partner protein termed von Willebrand factor type A interacting with AAA+ ATPase (ViaA). RavA-ViaA are functionally associated with anaerobic respirat…
View article: Dissecting the stability determinants of a challenging de novo protein fold using massively parallel design and experimentation
Dissecting the stability determinants of a challenging de novo protein fold using massively parallel design and experimentation Open
Designing entirely new protein structures remains challenging because we do not fully understand the biophysical determinants of folding stability. Yet, some protein folds are easier to design than others. Previous work identified the 43-r…
View article: Phosphorylation of the DNA repair scaffold SLX4 drives folding of the SAP domain and activation of the MUS81-EME1 endonuclease
Phosphorylation of the DNA repair scaffold SLX4 drives folding of the SAP domain and activation of the MUS81-EME1 endonuclease Open
The DNA repair scaffold SLX4 has multifaceted roles in genome stability, many of which depend on structure-selective endonucleases. SLX4 coordinates the cell cycle-regulated assembly of SLX1, MUS81-EME1, and XPF-ERCC1 into a tri-nuclease c…
View article: The MYC oncoprotein directly interacts with its chromatin cofactor PNUTS to recruit PP1 phosphatase
The MYC oncoprotein directly interacts with its chromatin cofactor PNUTS to recruit PP1 phosphatase Open
Despite MYC dysregulation in most human cancers, strategies to target this potent oncogenic driver remain an urgent unmet need. Recent evidence shows the PP1 phosphatase and its regulatory subunit PNUTS control MYC phosphorylation, chromat…
View article: Dissecting the stability determinants of a challenging de novo protein fold using massively parallel design and experimentation
Dissecting the stability determinants of a challenging de novo protein fold using massively parallel design and experimentation Open
Designing entirely new protein structures remains challenging because we do not fully understand the biophysical determinants of folding stability. Yet some protein folds are easier to design than others. Previous work identified the 43-re…
View article: Huntingtin structure is orchestrated by HAP40 and shows a polyglutamine expansion-specific interaction with exon 1
Huntingtin structure is orchestrated by HAP40 and shows a polyglutamine expansion-specific interaction with exon 1 Open
View article: The PNUTS-PAD domain recruits MYC to the PNUTS:PP1 phosphatase complex via the oncogenic MYC-MB0 region
The PNUTS-PAD domain recruits MYC to the PNUTS:PP1 phosphatase complex via the oncogenic MYC-MB0 region Open
Summary Despite MYC dysregulation in most human cancers, strategies to target this potent oncogenic driver remains an urgent unmet need. Recent evidence shows the PP1 phosphatase and its regulatory subunit PNUTS control MYC phosphorylation…
View article: Huntingtin structure is orchestrated by HAP40 and shows a polyglutamine expansion-specific interaction with exon 1
Huntingtin structure is orchestrated by HAP40 and shows a polyglutamine expansion-specific interaction with exon 1 Open
Supplementary Data files to accompany manuscript by Harding et al "Huntingtin structure is orchestrated by HAP40 and shows a polyglutamine expansion-specific interaction with exon 1" Supplementary Data 1 - Multiple sequence alignment for H…
View article: Huntingtin structure is orchestrated by HAP40 and shows a polyglutamine expansion-specific interaction with exon 1
Huntingtin structure is orchestrated by HAP40 and shows a polyglutamine expansion-specific interaction with exon 1 Open
Supplementary Data files to accompany manuscript by Harding et al "Huntingtin structure is orchestrated by HAP40 and shows a polyglutamine expansion-specific interaction with exon 1" Supplementary Data 1 - Multiple sequence alignment for H…
View article: HAP40 orchestrates huntingtin structure for differential interaction with polyglutamine expanded exon 1
HAP40 orchestrates huntingtin structure for differential interaction with polyglutamine expanded exon 1 Open
Huntington’s disease results from expansion of a glutamine-coding CAG tract in the huntingtin (HTT) gene, producing an aberrantly functioning form of HTT. Both wildtype and disease-state HTT form a hetero-dimer with HAP40 of unknown functi…
View article: Alternative splicing and allosteric regulation modulate the chromatin binding of UHRF1
Alternative splicing and allosteric regulation modulate the chromatin binding of UHRF1 Open
UHRF1 is an important epigenetic regulator associated with apoptosis and tumour development. It is a multidomain protein that integrates readout of different histone modification states and DNA methylation with enzymatic histone ubiquityla…
View article: The MLL1 trimeric catalytic complex is a dynamic conformational ensemble stabilized by multiple weak interactions
The MLL1 trimeric catalytic complex is a dynamic conformational ensemble stabilized by multiple weak interactions Open
Histone H3K4 methylation is an epigenetic mark associated with actively transcribed genes. This modification is catalyzed by the mixed lineage leukaemia (MLL) family of histone methyltransferases including MLL1, MLL2, MLL3, MLL4, SET1A and…
View article: Design and characterization of mutant and wildtype huntingtin proteins produced from a toolkit of scalable eukaryotic expression systems
Design and characterization of mutant and wildtype huntingtin proteins produced from a toolkit of scalable eukaryotic expression systems Open
View article: Backbone Assignments for human WDR5
Backbone Assignments for human WDR5 Open
View article: Design and characterisation of mutant and wild-type huntingtin proteins produced from a toolkit of scalable eukaryotic expression systems
Design and characterisation of mutant and wild-type huntingtin proteins produced from a toolkit of scalable eukaryotic expression systems Open
ABSTRACT: The pathogenic Huntington’s disease (HD) mutation causes polyglutamine (polyQ) tract expansion of the 348 kDa HTT protein above a critical threshold of ~35 glutamines. HD mutation effect on HTT is poorly understo…
View article: Design and characterisation of mutant and wild-type huntingtin proteins produced from a toolkit of scalable eukaryotic expression systems
Design and characterisation of mutant and wild-type huntingtin proteins produced from a toolkit of scalable eukaryotic expression systems Open
ABSTRACT: The pathogenic Huntington’s disease (HD) mutation causes polyglutamine (polyQ) tract expansion of the 348 kDa HTT protein above a critical threshold of ~35 glutamines. HD mutation effect on HTT is poorly understo…
View article: Design and characterisation of mutant and wild-type huntingtin proteins produced from a toolkit of scalable eukaryotic expression systems
Design and characterisation of mutant and wild-type huntingtin proteins produced from a toolkit of scalable eukaryotic expression systems Open
The gene mutated in Huntington’s disease (HD) patients encodes the 348 kDa huntingtin (HTT) protein. The pathogenic HD CAG-expansion mutation causes a polyglutamine (polyQ) tract at the N-terminus of the HTT protein to expand above a criti…
View article: Functional diversification of the NleG effector family in enterohemorrhagic <i>Escherichia coli</i>
Functional diversification of the NleG effector family in enterohemorrhagic <i>Escherichia coli</i> Open
The pathogenic strategy of Escherichia coli and many other gram-negative pathogens relies on the translocation of a specific set of proteins, called effectors, into the eukaryotic host cell during infection. These effectors act in concert …
View article: MLL1 minimal catalytic complex is a dynamic conformational ensemble susceptible to pharmacological allosteric disruption
MLL1 minimal catalytic complex is a dynamic conformational ensemble susceptible to pharmacological allosteric disruption Open
Histone H3K4 methylation is an epigenetic mark associated with actively transcribed genes. This modification is catalyzed by the mixed lineage leukaemia (MLL) family of histone methyltransferases including MLL1, MLL2, MLL3, MLL4, SET1A and…
View article: Conformational dynamics of the TTD–PHD histone reader module of the UHRF1 epigenetic regulator reveals multiple histone-binding states, allosteric regulation, and druggability
Conformational dynamics of the TTD–PHD histone reader module of the UHRF1 epigenetic regulator reveals multiple histone-binding states, allosteric regulation, and druggability Open
View article: Solution NMR structure of the TRIM21 B-box2 and identification of residues involved in its interaction with the RING domain
Solution NMR structure of the TRIM21 B-box2 and identification of residues involved in its interaction with the RING domain Open
Tripartite motif-containing (TRIM) proteins are defined by the sequential arrangement of RING, B-box and coiled-coil domains (RBCC), where the B-box domain is a unique feature of the TRIM protein family. TRIM21 is an E3 ubiquitin-protein l…
View article: Global analysis of protein folding using massively parallel design, synthesis, and testing
Global analysis of protein folding using massively parallel design, synthesis, and testing Open
Exploring structure space to understand stability Understanding the determinants of protein stability is challenging because native proteins have conformations that are optimized for function. Proteins designed without functional bias coul…
View article: Comparison of PHD domains of MLL5 and PHF13 proteins.
Comparison of PHD domains of MLL5 and PHF13 proteins. Open
Ribbon representation of the domains with superimposed backbone, MLL5PHD in blue and unbound PHF13PHD (PDB ID 3O70) in orange.
View article: Critical Assessment of automated Structure Determination of Proteins by NMR
Critical Assessment of automated Structure Determination of Proteins by NMR Open
The community-wide initiative "Critical Assessment of Automated Structure Determination of Proteins by NMR (CASD-NMR)" was launched in 2009 to to evaluate the ability of automated methods to produce 3D protein structures f…
View article: Critical Assessment of automated Structure Determination of Proteins by NMR
Critical Assessment of automated Structure Determination of Proteins by NMR Open
The community-wide initiative "Critical Assessment of Automated Structure Determination of Proteins by NMR (CASD-NMR)" was launched in 2009 to to evaluate the ability of automated methods to produce 3D protein structures f…
View article: The second round of Critical Assessment of Automated Structure Determination of Proteins by NMR: CASD-NMR-2013
The second round of Critical Assessment of Automated Structure Determination of Proteins by NMR: CASD-NMR-2013 Open
The second round of the community-wide initiative Critical Assessment of automated Structure Determination of Proteins by NMR (CASD-NMR-2013) comprised ten blind target datasets, consisting of unprocessed spectral data, assigned chemical s…