Mueller S

References (3)

Title : Structure of lipoprotein lipase in complex with GPIHBP1 - Arora_2019_Proc.Natl.Acad.Sci.U.S.A_116_10360
Author(s) : Arora R , Nimonkar AV , Baird D , Wang C , Chiu CH , Horton PA , Hanrahan S , Cubbon R , Weldon S , Tschantz WR , Mueller S , Brunner R , Lehr P , Meier P , Ottl J , Voznesensky A , Pandey P , Smith TM , Stojanovic A , Flyer A , Benson TE , Romanowski MJ , Trauger JW
Ref : Proc Natl Acad Sci U S A , 116 :10360 , 2019
Abstract : Lipoprotein lipase (LPL) plays a central role in triglyceride (TG) metabolism. By catalyzing the hydrolysis of TGs present in TG-rich lipoproteins (TRLs), LPL facilitates TG utilization and regulates circulating TG and TRL concentrations. Until very recently, structural information for LPL was limited to homology models, presumably due to the propensity of LPL to unfold and aggregate. By coexpressing LPL with a soluble variant of its accessory protein glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1) and with its chaperone protein lipase maturation factor 1 (LMF1), we obtained a stable and homogenous LPL/GPIHBP1 complex that was suitable for structure determination. We report here X-ray crystal structures of human LPL in complex with human GPIHBP1 at 2.5-3.0 A resolution, including a structure with a novel inhibitor bound to LPL. Binding of the inhibitor resulted in ordering of the LPL lid and lipid-binding regions and thus enabled determination of the first crystal structure of LPL that includes these important regions of the protein. It was assumed for many years that LPL was only active as a homodimer. The structures and additional biochemical data reported here are consistent with a new report that LPL, in complex with GPIHBP1, can be active as a monomeric 1:1 complex. The crystal structures illuminate the structural basis for LPL-mediated TRL lipolysis as well as LPL stabilization and transport by GPIHBP1.
ESTHER : Arora_2019_Proc.Natl.Acad.Sci.U.S.A_116_10360
PubMedSearch : Arora_2019_Proc.Natl.Acad.Sci.U.S.A_116_10360
PubMedID: 31072929
Gene_locus related to this paper: human-LPL

Title : NDRG1 overexpressing gliomas are characterized by reduced tumor vascularization and resistance to antiangiogenic treatment - Broggini_2016_Cancer.Lett_380_568
Author(s) : Broggini T , Wustner M , Harms C , Stange L , Blaes J , Thome C , Harms U , Mueller S , Weiler M , Wick W , Vajkoczy P , Czabanka M
Ref : Cancer Letters , 380 :568 , 2016
Abstract : Hypoxia-regulated molecules play an important role in vascular resistance to antiangiogenic treatment. N-myc downstream-regulated-gene 1 (NDRG1) is significantly upregulated during hypoxia in glioma. It was the aim of the present study to analyze the role of NDRG1 on glioma angiogenesis and on antiangiogenic treatment. Orthotopically implanted NDRG1 glioma showed reduced tumor growth and vessel density compared to controls. RT-PCR gene array analysis revealed a 30-fold TNFSF15 increase in NDRG1 tumors. Consequently, the supernatant from NDRG1 transfected U87MG glioma cells resulted in reduced HUVEC proliferation, migration and angiogenic response in tube formation assays in vitro. This effect was provoked by increased TNFSF15 promoter activity in NDRG1 cells. Mutations in NF-kappaB and AP-1 promoter response elements suppressed TNFSF15 promoter activity. Moreover, U87MG glioma NDRG1 knockdown supernatant contained multiple proangiogenic proteins and increased HUVEC spheroid sprouting. Sunitinib treatment of orhotopically implanted mice reduced tumor volume and vessel density in controls; in NDRG1 overexpressing cells no reduction of tumor volume or vessel density was observed. NDRG1 overexpression leads to reduced tumor growth and angiogenesis in experimental glioma via upregulation of TNFSF15. In NDRG1 overexpressing glioma antiangiogenic treatment does not yield a therapeutic response.
ESTHER : Broggini_2016_Cancer.Lett_380_568
PubMedSearch : Broggini_2016_Cancer.Lett_380_568
PubMedID: 26297987

Title : On the routine use of soft X-rays in macromolecular crystallography. Part IV. Efficient determination of anomalous substructures in biomacromolecules using longer X-ray wavelengths - Mueller-Dieckmann_2007_Acta.Crystallogr.D.Biol.Crystallogr_63_366
Author(s) : Mueller-Dieckmann C , Panjikar S , Schmidt A , Mueller S , Kuper J , Geerlof A , Wilmanns M , Singh RK , Tucker PA , Weiss MS
Ref : Acta Crystallographica D Biol Crystallogr , 63 :366 , 2007
Abstract : 23 different crystal forms of 19 different biological macromolecules were examined with respect to their anomalously scattering substructures using diffraction data collected at a wavelength of 2.0 A (6.2 keV). In more than 90% of the cases the substructure was found to contain more than just the protein S atoms. The data presented suggest that chloride, sulfate, phosphate or metal ions from the buffer or even from the purification protocol are frequently bound to the protein molecule and that these ions are often overlooked, especially if they are not bound at full occupancy. Thus, in order to fully describe the macromolecule under study, it seems desirable that any structure determination be complemented with a long-wavelength data set.
ESTHER : Mueller-Dieckmann_2007_Acta.Crystallogr.D.Biol.Crystallogr_63_366
PubMedSearch : Mueller-Dieckmann_2007_Acta.Crystallogr.D.Biol.Crystallogr_63_366
PubMedID: 17327674
Gene_locus related to this paper: manes-hnl