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Journal Issue - Volume 18 Issue 11 (November 2009)

  • In this issue

  • Published in Wiley Interscience on Oct 23, 2009
  • DOI: 10.1002/pro.271 (p n/a-n/a)

Abstract Methuselah (Mth) is a G protein‐coupled receptor (GPCR) associated with longevity in Drosophila melanogaster. Previously, Stunted (Sun) was identified as a peptide agonist of Mth. Here, we identify two additional activators of Mth signaling: Drosophila Sex Peptide (SP) and a novel peptide (Serendipitous Peptide Activator of Mth, SPAM). Minimal functional sequences and key residues were identified from Sun and SPAM by studying...

Abstract Human coronavirus OC43 (HCoV‐OC43) is one of the causes of the “common cold” in human during seasons of cold weather. The primary function of the HCoV‐OC43 nucleocapsid protein (N protein) is to recognize viral genomic RNA, which leads to ribonucleocapsid formation. Here, we characterized the stability and identified the functional regions of the recombinant HCoV‐OC43 N protein. Circular dichroism and fluorescence...

Abstract Integration of HIV‐1 cDNA into the host genome is a crucial step for viral propagation. Two nucleotides, cytosine and adenine (CA), conserved at the 3′ end of the viral cDNA genome, are cleaved by the viral integrase (IN) enzyme. As IN plays a crucial role in the early stages of the HIV‐1 life cycle, substrate blockage of IN is an attractive strategy for therapeutic interference. In this study, we used the 2‐LTR‐circle...

Abstract Protein aggregation is a common feature of late onset neurodegenerative disorders, including Alzheimer's disease. In Alzheimer's disease, misassembly of the Aβ peptide is genetically linked to proteotoxicity associated with disease etiology. A reduction in Aβ proteotoxicity is accomplished, in part, by the previously reported Aβ disaggregation and proteolysis activities–under partial control of heat shock factor 1, a...

Abstract Two structurally‐related members of the lysosomal mannosidase family, the broad substrate specificity enzyme human lysosomal α‐mannosidase (hLM, MAN2B1) and the human core α‐1, 6‐specific mannosidase (hEpman, MAN2B2) act in a complementary fashion on different glycosidic linkages, to effect glycan degradation in the lysosome. We have successfully expressed these enzymes in Drosophila S2 cells and functionally characterized...

Abstract In eukaryotic replication licensing, Cdt1 plays a key role by recruiting the MCM2‐7 complex onto the origin of chromosome. The C‐terminal domain of mouse Cdt1 (mCdt1C), the most conserved region in Cdt1, is essential for licensing and directly interacts with the MCM2‐7 complex. We have determined the structures of mCdt1CS (mCdt1C_small; residues 452 to 557) and mCdt1CL (mCdt1C_large; residues 420 to 557) using X‐ray...

Abstract Fas‐associated factor (FAF)‐1 is a multidomain protein that was first identified as a member of the Fas death‐inducing signaling complex, but later found to be involved in various biological processes. Although the exact mechanisms are not clear, FAF1 seems to play an important role in cancer, asbestos‐induced mesotheliomas, and Parkinson's disease. It interacts with polyubiquitinated proteins, Hsp70, and p97/VCP...

Abstract Domain 4 of the anthrax protective antigen (PA) plays a key role in cellular receptor recognition as well as in pH‐dependent pore formation. We present here the 1.95 Å crystal structure of domain 4, which adopts a fold that is identical to that observed in the full‐length protein. We have also investigated the structural properties of the isolated domain 4 as a function of pH, as well as the pH‐dependence on binding to the...

Abstract RNA polymerase (RNAP) is an essential and highly conserved enzyme in all organisms. The process of transcription initiation is fundamentally different between prokaryotes and eukaryotes. In prokaryotes, initiation is regulated by σ factors, making the essential interaction between σ factors and RNAP an attractive target for antimicrobial agents. Our objective was to achieve the first step in the process of developing novel...

Abstract The liver‐specific organic anion transporting polypeptides OATP1B1 and OATP1B3 are highly homologous and share numerous substrates. However, at low concentrations OATP1B1 shows substrate selectivity for estrone‐3‐sulfate. In this study, we investigated the molecular mechanism for this substrate selectivity of OATP1B1 by constructing OATP1B1/1B3 chimeric transporters and by site‐directed mutagenesis. Functional studies of...

Abstract Deletion analysis and alanine‐scanning based on a homology‐based interaction model were used to identify determinants of oligomerization in the transcriptional regulator CynR, a member of the LysR‐type transcriptional regulator (LTTR) family. Deletion analysis confirmed that the putative regulatory domain of CynR was essential for driving the oligomerization of λ repressor‐CynR fusion proteins. The interaction surface of a...

Abstract A single plasmid that allows controlled coexpression has been developed for use in mycobacteria. The tetracycline inducible promoter, PtetO, was used to provide tetracycline‐dependent induction of one gene, while the Psmyc, Pimyc, or Phsp promoters were used to provide three different levels of constitutive expression of a second gene. The functions of these four individual promoters were established using green fluorescent...

Abstract Crystal structures of Gαi (and closely related family member Gαt) reveal much of what we currently know about G protein structure, including changes which occur in Switch regions. Gαt exhibits a low rate of basal (uncatalyzed) nucleotide exchange and an ordered Switch II region in the GDP‐bound state, unlike Gαi, which exhibits higher basal exchange and a disordered Switch II region in GαiGDP structures. Using purified Gαi and Gαt, we examined the...

Abstract Methamphetamine (METH) is a major drug threat in the United States and worldwide. Monoclonal antibody (mAb) therapy for treating METH abuse is showing exciting promise and the understanding of how mAb structure relates to function will be essential for future development of these important therapies. We have determined crystal structures of a high affinity anti‐(+)‐METH therapeutic single chain antibody fragment (scFv6H4,...

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