共查询到20条相似文献,搜索用时 15 毫秒
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Petrescu AD Hertz R Bar-Tana J Schroeder F Kier AB 《The Journal of biological chemistry》2005,280(17):16714-16727
The F-domain of rat HNF-4alpha1 has a crucial impact on the ligand binding affinity, ligand specificity and secondary structure of HNF-4alpha. (i) Fluorescent binding assays indicate that wild-type, full-length HNF-4alpha (amino acids 1-455) has high affinity (Kd=0.06-12 nm) for long chain fatty acyl-CoAs (LCFA-CoA) and low affinity (Kd=58-296 nm) for unesterified long chain fatty acids (LCFAs). LCFA-CoA binding was due to close molecular interaction as shown by fluorescence resonance energy transfer (FRET) from full-length HNF-4alpha tryptophan (FRET donor) to bound cis-parinaroyl-CoA (FRET acceptor), which yielded an intermolecular distance of 33 A, although no FRET to cis-parinaric acid was detected. (ii) Deleting the N-terminal A-D-domains, comprising the AF1 and DNA binding functions, only slightly affected affinities for LCFA-CoAs (Kd=0.9-4 nm) and LCFAs (Kd=93-581 nm). (iii) Further deletion of the F-domain robustly reduced affinities for LCFA-CoA and reversed ligand specificity (i.e. high affinity for LCFAs (Kd=1.5-32 nm) and low affinity for LCFA-CoAs (Kd=54-302 nm)). No FRET from HNF-4alpha-E (amino acids 132-370) tryptophan (FRET donor) to bound cis-parinaroyl-CoA (FRET acceptor) was detected, whereas an intermolecular distance of 28 A was calculated from FRET between HNF-4alpha-E and cis-parinaric acid. (iv) Circular dichroism showed that LCFA-CoA, but not LCFA, altered the secondary structure of HNF-4alpha only when the F-domain was present. (v) cis-Parinaric acid bound to HNF-4alpha with intact F-domain was readily displaceable by S-hexadecyl-CoA, a nonhydrolyzable thioether analogue of LCFA-CoAs. Truncation of the F-domain significantly decreased cis-parinaric acid displacement. Hence, the C-terminal F-domain of HNF-4alpha regulated ligand affinity, ligand specificity, and ligand-induced conformational change of HNF-4alpha. Thus, characteristics of F-domain-truncated mutants may not reflect the properties of full-length HNF-4alpha. 相似文献
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Structure/function studies of hepatocyte nuclear factor-1alpha, a diabetes-associated transcription factor 总被引:1,自引:0,他引:1
Yang Q Yamagata K Yamamoto K Miyagawa J Takeda J Iwasaki N Iwahashi H Yoshiuchi I Namba M Miyazaki J Hanafusa T Matsuzawa Y 《Biochemical and biophysical research communications》1999,266(1):196-202
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Modulation of transcriptional activation and coactivator interaction by a splicing variation in the F domain of nuclear receptor hepatocyte nuclear factor 4alpha1. 下载免费PDF全文
Frances M. Sladek Michael D. Ruse Jr. Luviminda Nepomuceno Shih-Ming Huang Michael R. Stallcup 《Molecular and cellular biology》1999,19(10):6509-6522
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SREBP-1 interacts with hepatocyte nuclear factor-4 alpha and interferes with PGC-1 recruitment to suppress hepatic gluconeogenic genes 总被引:12,自引:0,他引:12
Yamamoto T Shimano H Nakagawa Y Ide T Yahagi N Matsuzaka T Nakakuki M Takahashi A Suzuki H Sone H Toyoshima H Sato R Yamada N 《The Journal of biological chemistry》2004,279(13):12027-12035
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Thioesterase activity and acyl-CoA/fatty acid cross-talk of hepatocyte nuclear factor-4{alpha} 总被引:2,自引:0,他引:2
Hertz R Kalderon B Byk T Berman I Za'tara G Mayer R Bar-Tana J 《The Journal of biological chemistry》2005,280(26):24451-24461
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Polymorphisms of the HNF1A gene encoding hepatocyte nuclear factor-1 alpha are associated with C-reactive protein 下载免费PDF全文
Reiner AP Barber MJ Guan Y Ridker PM Lange LA Chasman DI Walston JD Cooper GM Jenny NS Rieder MJ Durda JP Smith JD Novembre J Tracy RP Rotter JI Stephens M Nickerson DA Krauss RM 《American journal of human genetics》2008,82(5):1193-1201
Data from the Pharmacogenomics and Risk of Cardiovascular Disease (PARC) study and the Cardiovascular Health Study (CHS) provide independent and confirmatory evidence for association between common polymorphisms of the HNF1A gene encoding hepatocyte nuclear factor-1 alpha and plasma C-reactive protein (CRP) concentration. Analyses with the use of imputation-based methods to combine genotype data from both studies and to test untyped SNPs from the HapMap database identified several SNPs within a 5 kb region of HNF1A intron 1 with the strongest evidence of association with CRP phenotype. 相似文献
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