Biomedical subjects

Yun Li

Publications and source records attributed to Yun Li.

At least 55 records · Page 3Linked to original sources

PubMed2006

[Cloning and analysis of genes in the halocin C8 gene cluster].

Halocin C8 (HalC8), produced by a halophilic archaeon strain AS7092, is a gene-coded peptide microhalocin and has a wide inhibitory spectrum against the members of haloarchaea. To investigate the mechanisms of the gene expression regulation, the peptide processing and transportation of this halocin, a 9.3kb DNA gene cluster containing the halocin C8 encoding gene (proC8) and other possible involved genes was cloned, by screening of a genomic library of AS7092 as well as anchoring PCR technique. Sequence analysis indicated that it contained at least six open reading frames, including halU, halR, proC8, halT1, halT2 and halT3. The gene halU encodes a membrane-spanning protein HalU, but its function is unknown. The gene halR encodes a putative regulator protein HalR, its function was deduced to regulate the transcription of proC8 gene, which encodes the precursor for halocin C8. The gene halT1, halT2 and halT3 likely encode the transporters HalT1, HalT2 and HalT3, the functions of which were speculated to transport the halocin C8 out of the cellular membrane. This is the first report of gene cluster cloning for any halocin.

Amino Acid Sequence↗

PubMed2006

[Screening of new HIV inhibitors based on the database of traditional Chinese medicine].

AIM: To report the preliminary result of the HIV inhibitor screening based on cheminformatics tools and the traditional Chinese medicine database. METHODS: Database search was carried out with saquinavir molecule as a template, further screening was made with docking. Detailed studies using molecular dynamics simulation of 50 ps and 200 ps were made with respect to a potential leading compound, leucovorin. RESULTS: The leucovorin molecule distinguished from other molecules as a potential drug candidate and is subject to extensive studies. The bonding profile and energy were calculated with MD simulations. CONCLUSION: Our results could be very helpful when we modify leucovorin or design new inhibitors against HIV.

Anti-HIV Agents↗

PubMed2006

[Chronic effects of low-dose hydrochlorothiazide in patients with mild to moderate essential hypertension].

OBJECTIVE: To investigate the chronic efficacy of low-dose hydrochlorothiazide (HCTZ) in patients with mild-to-moderate hypertension. METHODS: After a 2-weeks placebo run-in period, 232 patients with mild or moderate hypertension were recruited and received HCTZ (12.5 mg once daily) therapy for one year. Patient compliance and blood pressure were monitored and serum BUN, Cr, glucose, electrolytes, and lipids were measured before, 6 weeks and 1 year after treatment. RESULTS: (1) Reduction of SBP, DBP and MAP were more significantly at 1 year [(10.45 +/- 17.28) mm Hg, (8.45 +/- 11.06) mm Hg, (9.12 +/- 10.88) mm Hg] than that at 6 weeks post therapy [(6.01 +/- 16.05) mm Hg, (2.90 +/- 10.33) mm Hg, (3.94 +/- 10.68) mm Hg, all P < 0.05]. Blood pressure were reduced to normal in 35.1% patients at 1 year and in 20.3% patients at 6 weeks (P < 0.05). (2) No patient developed diabetes mellitus or hypokalemia during therapy while the serum uric acid at 1 year post therapy was significantly higher than that at before therapy (P < 0.05). CONCLUSION: The study indicates that low dose HCTZ is an effective and safe antihypertensive agent for patients with mild-to-moderate hypertension and uric acid changes during therapy need to be monitored.

Adult↗

PubMed2006

[Establishment and evaluation of a computer-based software system for detection of initial approximal caries].

OBJECTIVE: To establish and evaluate a computer-based software system (caries diagnosing system, CDS): CDS for better detection of initial approximal caries based on the performance of radiography. METHODS: A total of 190 approximal surfaces from 95 extracted posterior teeth were examined by bite-wing radiography. After analysing and extracting the approximal lesion's characteristics of X-ray performance, using Matlab and VC language, the CDS was established. Then the proximal surfaces of these teeth were detected automatically by CDS, and scored by naked eyes of 8 experienced dentists for the extent of lesions. The histological appearance of sectioned teeth was used as the gold standard to assess sensitivity, specificity, accuracy, and reproducibility. RESULTS: The sensitivity of CDS was 0.728, Pearson's correlation was 0.722, better than that of optic estimation. The reproducibility of CDS was good too. CONCLUSIONS: The CDS can report the lesion site and extension, its diagnostic level is better than that of optic estimation, it is an reasonably sensitive and accurate method for the detection of initial approximal caries in present clinic practice, and a tool of providing objective data.

Dental Caries↗

PubMed2006

[Evaluation on birth defects surveillance system in four counties of Shanxi province, China].

OBJECTIVE: To evaluate the reliability of the birth defects surveillance system in four counties with high prevalence of birth defects (Pingding, Xiyang, Taigu and Zezhou counties) in Shanxi province, China. METHODS: One township was selected from each county as study site. The health workers chosen from township or village level were trained to visit families on the outcomes of each pregnancy who gave birth during year 2003 in the study site. The number of births and cases collected in the study were compared with that from the surveillance system. The number of births reported by surveillance system in four counties was also compared with the data from the local government. The criteria of evaluation were: 1) number of the missing report of births should < or = 5%, 2) the number of missing report on major external birth defects cases should < or = 10%. Researchers from the Peking University were responsible for examining the quality of surveillance in some terminal units of surveillance system. RESULTS: The numbers of births reported in the study and from the surveillance system for four-township were 1043 and 997, respectively. 46 births were missing and the rate of misreporting for births was 4.4%. The numbers of birth defects cases reported in the study and from the surveillance system were 30 and 29, respectively. 1 case of birth defect as missed, and rate of misreporting for birth defects cases was 3.3%. The total number of births reported from surveillance was similar to that in the study in four counties, with a difference of 1.2%. Birth registry data was rather readable and special health workers responsible for surveillance work were present in all the terminal units of the surveillance system. CONCLUSION: The misreporting of births and cases existed in the birth defects surveillance system of the four counties in Shanxi province, but were lower than the allowable criteria. The surveillance units had better registration, reporting and administration of births and birth defect cases. Hence, the quality of the data from the surveillance system in these four counties was reliable.

Birth Certificates↗

PubMed2006

[Cytological and embryological observation on the cross of autotriploid x diploid in rice].

In this report, the process of hybridization between different ploidy levels was observed in rice. Autotriploid (2n = 36) 149-B, generated naturally from the twin-seedling rice population SAR-2, was used as the female parent crossing with a normal diploid variety Shuhui 363. The processes of fertilization and embryological development were investigated. The pollen could germinate in triploid tissue of pistil normally and arrive at micropyle. But the percentage of double fertilization was only 8.89%, and the percentage of seed setting was 0.566%. The hybridization obstacles mainly occurred in the process of fertilization. Barriers of double fertilization, prolongation and abnormal development of proembryo, and even development stopping or differentiation failure of embryo and/or endosperm could result in abnormal development and abortion of zygote.

Diploidy↗

PubMed2006

[Construction and expression of eukaryotic expression plasmid containing rat TCR Vbeta8.2 gene].

AIM: To construct the recombinant eukaryotic expression vector pTARGET-TCR Vbeta8.2 and detect its their expression. METHODS: Gene encoding TCR Vbeta8.2 was amplified by RT-PCR from spleen cells of Lewis rats, and then cloned into eukaryotic expression vector pTARGET. Recombinant clones were identified by blue/white screening on indicator plates after transformed into E.coli strain JM109, and then by bacteria colonies PCR and DNA sequencing. Recombinant plasmid was injected into BALB/c mice intramuscularly. Then the injected skeletal muscle was isolated, and expression of TCR Vbeta8.2 gene was detected by RT-PCR and immunohistochemistry. Immunocytochemical staining was used to detect the expression of pTARGET-TCR Vbeta8.2 gene after the recombinant plasmid was transfected into COS-7 cells by lipofectamine. RESULTS: DNA sequencing demonstrated that TCR Vbeta8.2 gene was successfully inserted into pTARGET. RT-PCR demonstrated that TCR Vbeta;8.2 gene was successfully expressed in the injected muscle. Immunohistochemistry staining showed the expression of recombinant plasmid in the transfected COS-7 cells. CONCLUSION: The eukaryotic expression vector pTARGET-TCR Vbeta8.2 was successfully constructed and expressed in vivo and vitro, which would lay foundation for further studies on the protective effects of TCR Vbeta DNA vaccine on CIA.

Animals↗

PubMed2006

[Drought tolerance of transgenic sweet potato expressing both Cu/Zn superoxide dismutase and ascorbate peroxidase].

Two strains, Cu/Zn SOD and APX gene transferred sweet potato (TS) and non-transgenic sweet potato (Ipomoea batatas L.) (NT), were used as experimental materials to study the drought tolerance under three different degrees of water stress: 0, -0.44 MPa, -0.78 MPa. The results showed that activities of Cu/Zn SOD and APX increased under -0.44 MPa and decreased under -0.78 MPa (Fig. 2), P(n), G(s) and leaf water content decreased, C(i) increased, then decreased under water stress (Fig. 6), but under the same PEG concentration all these indexes in the TS were higher than those in NT. The accumulation of H(2)O(2) and O(-*)(2) (Fig. 1) increased the degree of lipid peroxidation of the plasma membrane (Fig. 4), prompted the accumulation of MDA (Fig. 3), and the accumulation of TS always lower than the NT at the same PEG concentration. All the results showed that the transgenic sweet potato has a stronger ability to clean up active oxygen than the non-transgenic one, and it can keep a higher leaf water content and P(n) under water stress, so it has a stronger tolerance to drought.

Adaptation, Physiological↗

PubMed2006

[Self hearing recovery in infants with hearing loss after universal newborn hearing screening system].

OBJECTIVE: To analyze the reasons of hearing recovery of newborns and infants which were diagnosed hearing loss within 3 months old by universal newborn hearing screening (UNHS) system. METHOD: Newborns and infants born from Nov. 2001 to Jun. 2005 in Shanghai who failed UNHS were studied. Audiometric evaluations were performed in Shanghai Children's Hearing and Speech Center. Those with hearing loss were diagnosed within 3 months old and were followed-up at least 6 months. Analysis was carried out targeting for hearing recovery cases. RESULT: Six hundred and eighty-one cases failed the UNHS and were confirmed hearing loss within 3 months old. During the 6-24 months period of followed-up, 94 (13.8%) of 681 infants caught normal hearing. Among these 94 infants(115 ears), otitis media with effusion was found in 56 cases (59.6%), no reasonable cause was found in the other 38 cases (40.4%). Among the 115 ears which recovered to normal, there were 105 ears (91.3%) with primary diagnosis of mild hearing loss, 8 ears (7.0%) with moderate hearing loss and 2 ears (1.7%) with moderate-severe hearing loss. No recovery was found in the cases with primary diagnosis of severe and profound hearing loss. CONCLUSION: Newborns and infants with hearing loss diagnosed within 3 months old have possibility to recover as they are growing. The critical reasons might be self-recovery from otitis media with effusion and outcomes of central auditory system development.

Audiometry↗

PubMed2006

[Desensitization of dust mite drops on antigen-specific asthmatic reaction in guinea pigs].

AIM: To establish an antigen-specific asthmatic model of guinea pig induced by protein antigen extracted from Dermatophagoides farinae (Der f), and study the desensitization of dust mite drops (DMD, extracted from Der f) in a dose progressive manner and long-term sublingual administration. METHODS: To sensitize the guinea pigs, the protein antigen emulsified in aluminium hydroxide gel was subcutaneously and intraperitoneally injected. To observe early-phase reaction of asthma, lung resistance (R(L)) and lung dynamic compliance (Cdyn) in the sensitized guinea pigs were determined by intravenously injecting antigen. To observe late-phase reaction of asthma, the sensitized guinea pigs were challenged with aerosolized antigen for 7 days. Subsequently, methacholine (Mch) in a cumulative dose-manner induced-airway hyperreactivity (AHR), inflammatory cells numbers in bronchoalveolar lavage fluid (BALF) and pathological changes of lung tissue were measured in the model. From the first day of sensitization, the guinea pigs in treatment group sublingually received DMD in a dose progressive manner. The model group sublingually received equivalent saline. The normal control group did not receive any treatment. RESULTS: The guinea pigs in model group showed a significant increase in R(L) and decrease in Cdyn, and developed a marked AHR to Mch. The number of total leukocytes and eosinophils increased significantly in BALF. Serious infiltration of eosinophils was observed in pathological section of lung tissue. Compared with model group, DMD treatment group exhibited a significant amelioration for early-phase and late-phase reaction of asthma. CONCLUSION: DMD in a dose progressive manner and long-term sublingual administration displays a significant desensitization on Der f antigen-specific asthmatic reaction. The results provided experimental evidence for clinical therapy.

Administration, Sublingual↗

PubMed2006

[Application of HPLC fingerprint in quality control of Fufangteng combination formula].

OBJECTIVE: To establish the characteristic mode of HPLC fingerprint of Fufangteng combination formula for the quality control of this medicine. METHOD: 10 batch certified products were selected to establish the characteristic mode of HPLC fingerprint of Fufangteng combination formula by chromatographic pattern matching and retention time correction. RESULT: This characteristic mode of HPLC fingerprint can clearly differentiate the eligible Fufangteng products from the unqualified products. CONCLUSION: This method can provide thorough information for the quality control of Fufangteng combination formula.

Administration, Oral↗

PubMed2006

[Profiles of sediment porewater nutrient concentrations on tidal flat of turbidity maximum zone in Changjiang (Yangtze River) estuary].

Profiles of nutrients (i.e., NH4+, NO2-, NO3-, PO4(3-), and SiO3(2-)) in porewater of sediment were investigated monthly in the intertidal flat of Chongming Dongtan in Changjiang (Yangtze River) estuary during March 2005 to February 2006. The results indicate that concentrations of NH4+ and SiO3(2-) in porewater are always in the range of 200 micromol/L to 500 micromol/L and show different patterns of distribution profile among high, middle, and low marshes. Compared to high and middle marsh, low marsh, without vegetation coverage and of coarser grain size, generally contains higher NH4+ and lower SiO3(21) concentrations. SiO3(2-) concentrations are predominantly determined by seasonal temperature change, but variations of NH4+ are more complicated and prone to exhibit lower values in spring and summer when the vegetation above show relatively high growth rate. Concentrations of NO2- + NO3- and PO4(3-) in porewater are commonly much lower than NH4+ and SiO3(2-) by 2 to 3 orders of magnitude, however, due to factors such as bioturbation, the concentrations in top sediment may be higher than 10 micromol/L. The relatively high NO3- concentration in top sediment,together with the rapid transfer from oxygenic to anoxic environment, make it possible that significant denitrification happens, which may draw its remarkable influence on the biogeochemical cycles of nutrient elements in the land-sea interaction area in Changjiang (Yangtze River) estuary.

China↗

PubMed2006

[Effect of recombinant human growth hormone on glucose metabolism in children with growth hormone deficiency].

OBJECTIVE: Numerous studies in children with growth hormone deficiency (GHD) show that recombinant human growth hormone (rhGH) treatment results in significant catch-up growth, but some papers reported that the children who underwent rhGH therapy might be at increased risk of diabetes. The aim of this study was to investigate the effects of rhGH treatment on blood glucose and insulin metabolism in children with GHD and the relationship between growth hormone (GH) and glucose homeostasis. METHODS: In this study, 44 children with GHD treated with rhGH [0.1 U/(kgxd)] and age- and sex-matched 20 healthy children were enrolled. The GHD group included 28 males and 16 females aged from 4.5 to 16.5 years (mean 10.4 +/- 2.6 years), including 18 cases of complete GHD and 26 cases of partial GHD. The sexual development stage of all subjects was in Tanner I. Oral glucose tolerance tests (OGTT) were done, and body mass index (BMI), serum insulin-like growth factor-1 (IGF-1) level and insulin resistance by homeostasis model (HOMA-IR) were measured at the time of diagnosis and every 3 months after rhGH therapy. Continuous glucose monitoring system (CGMS) was applied for two cases with hyperglycemia. RESULTS: (1) Fasting glucose and IGF-1 levels increased since 3 months of treatment and did not decrease since then. The levels of fasting glucose and IGF-1 at every time points of rhGH therapy were higher than the levels at the time of diagnosis (F = 6.81, P < 0.01; F = 7.31, P < 0.01, respectively). HOMA-IR and fasting insulin levels were increased since 3 and 9 months of treatment (P = 0.001 and P = 0.021, respectively). They decreased after 12 months of therapy and the levels at 18 months of therapy were similar to that at diagnosis. (2) Pearson correlation analysis showed that HOMA-IR was positively correlated with BMI, IGF-1 and the duration of treatment (r = 0.251, 0.437, 0.281, P < 0.01, respectively). The curve between HOMA-IR and duration of therapy was similar with parabola and the quadratic equation obtained was as follows: HOMA-IR = 1.5048 + 0.2177 x duration of therapy (months)-0.0103 x duration of therapy (months)(2) (r(2) = 0.147, F = 14.16, P < 0.01). (3) Two cases had transitory hyperglycemia. Their fasting glucose levels were all higher than 7.1 mmol/L. The glucose levels returned to normal after 1 month and 5 days respectively. OGTT and CGMS showed that their plasma glucose levels were normal after rhGH therapy was applied again. CONCLUSION: The children who underwent rhGH therapy may be at increased risk of insulin resistance (especially during the first year) and the therapy may even induce transitory glucose metabolic disorder in a very small proportion of patients. Circulating IGF-1 may participate in the control of insulin sensitivity and play an important role in the hormonal balance between GH and insulin. It may be necessary to monitor glucose metabolism and IGF-1 for all children who are treated with rhGH therapy.

Adolescent↗

PubMed2005

Polycystin 2 interacts with type I inositol 1,4,5-trisphosphate receptor to modulate intracellular Ca2+ signaling.

Autosomal dominant polycystic kidney disease, a common cause of renal failure, arises from mutations in either the PKD1 or the PKD2 gene. The precise function of both PKD gene products polycystins (PCs) 1 and 2 remain controversial. PC2 has been localized to numerous cellular compartments, including the endoplasmic reticulum, plasma membrane, and cilia. It is unclear what pools are the most relevant to its physiological function as a putative Ca2+ channel. We employed a Xenopus oocyte Ca2+ imaging system to directly investigate the role of PC2 in inositol 1,4,5-trisphosphate (IP3)-dependent Ca2+ signaling. Cytosolic Ca2+ signals were recorded following UV photolysis of caged IP3 in the absence of extracellular Ca2+. We demonstrated that overexpression of PC2, as well as type I IP3 receptor (IP3R), significantly prolonged the half-decay time (t1/2) of IP3-induced Ca2+ transients. However, overexpressing the disease-associated PC2 mutants, the point mutation D511V, and the C-terminally truncated mutation R742X did not alter the t1/2. In addition, we found that D511V overexpression significantly reduced the amplitude of IP3-induced Ca2+ transients. Interestingly, overexpression of the C terminus of PC2 not only significantly reduced the amplitude but also prolonged the t1/2. Co-immunoprecipitation assays indicated that PC2 physically interacts with IP3R through its C terminus. Taken together, our data suggest that PC2 and IP3R functionally interact and modulate intracellular Ca2+ signaling. Therefore, mutations in either PC1 or PC2 could result in the misregulation of intracellular Ca2+ signaling, which in turn could contribute to the pathology of autosomal dominant polycystic kidney disease.

Animals↗

PubMed2005

Relationship between risk stratification by cardiac troponin level and adherence to guidelines for non-ST-segment elevation acute coronary syndromes.

BACKGROUND: The threshold of troponin elevation that stimulates changes in clinical decision making for patients with non-ST-segment elevation acute coronary syndromes (NSTE ACSs) has not been previously evaluated. METHODS: A total of 23 298 patients with NSTE ACSs from the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines) initiative were separated into categories of maximum troponin ratios (ratio of the highest recorded troponin value in the first 24 hours to the local laboratory troponin assay upper limit of normalization [ULN]). RESULTS: Unadjusted rates of in-hospital mortality increased from the group with troponin levels below the reference limit (maximum troponin ratio 0-1 x ULN; n = 5291) to those with minor (1-2 x ULN; n = 2499), intermediate (2-5 x ULN; n = 3825), and major (>5 x ULN; n = 11 683) elevations (-2.8% vs 4.6% vs 4.7% vs 6.0%). The use of early (<24 hours) aspirin, heparin, glycoprotein IIb/IIIa inhibitors, and beta-blockers was similar for the group with troponin levels below the reference limit compared with those with minor troponin elevations, and greater use of medications was demonstrated in patients with intermediate and major troponin elevations. Use of cardiac catheterization and percutaneous coronary intervention was higher in patients with troponin levels below the reference limit compared with those with minor troponin elevations, and procedures were used most frequently in patients with major troponin elevations. Similar patterns of care were demonstrated after excluding patients with chronic renal insufficiency. CONCLUSIONS: Any degree of troponin elevation is associated with a higher risk of mortality for patients with NSTE ACSs, but guideline-recommended medical therapies are used more commonly only in patients with intermediate and major troponin elevations, whereas patients with troponin levels below the reference limit underwent invasive procedures more frequently than those with mild troponin elevations.

Acute Disease↗

PubMed2005

Monoclonal antibodies developed for detection of an epizootic virus associated with mass mortalities of cultured scallop Chlamys farreri.

Recently, an enveloped, spherical RNA virus was identified as the causative agent of mass mortalities among adult scallop Chlamys farreri, which is cultured on the northern coast of China. Hybridomas were prepared from mice immunized with highly purified virions. Four stable hybridomas secreting monoclonal antibodies (MAbs) of IgG isotype were obtained after screening by means of enzyme-linked immunosorbent assay (ELISA) and immunofluorescence assay (IFA). The specificity of the MAbs to this virus was confirmed by immunogold electron microscopy (IEM). All the selected MAbs recognized epitopes on the envelope spikes of the virions. Subsequently, the MAbs were used for in situ immunofluorescent detection of the virus in Davidson's fixed tissue sections. The results showed that the fluorescent cells were mostly observed in epithelia of different organs, but not in the epithelium of the digestive diverticulae. Cytopathological changes and focal lesions corresponding to virus-positive cells were clearly recognized in the affected epithelia, revealing a potential role of this virus in pathogenesis.

Animals↗

PubMed2005

Clinical and economic implications of the Multicenter Automatic Defibrillator Implantation Trial-II.

BACKGROUND: The Multicenter Automatic Defibrillator Implantation Trial (MADIT)-II demonstrated that implantable cardioverter defibrillators (ICDs) save lives when used in patients with a history of myocardial infarction (MI) and an ejection fraction of 0.3 or less. OBJECTIVE: To investigate the cost-effectiveness of implanting ICDs in patients who met MADIT-II eligibility criteria and were enrolled in the Duke Cardiovascular Database between 1 January 1986 and 31 December 2001. DESIGN: Cost-effectiveness analysis. DATA SOURCES: Published literature, databases owned by Duke University Medical Center, and Medicare data. TARGET POPULATION: Adults with a history of MI and an ejection fraction of 0.3 or less. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTIONS: ICD therapy versus conventional medical therapy. OUTCOMES MEASURES: Cost per life-year gained and incremental cost-effectiveness. RESULTS: Compared with conventional medical therapy, ICDs are projected to result in an increase of 1.80 discounted years in life expectancy and an incremental cost-effectiveness ratio of 50,500 dollars per life-year gained. Cost-effectiveness varied dramatically with changes in time horizon: The cost-effectiveness ratio increased to 67,800 dollars per life-year gained, 79,900 dollars per life-year gained, 100,000 dollars per life-year gained, 167,900 dollars per life-year gained, and 367,200 dollars per life-year gained for 15-year, 12-year, 9-year, 6-year, and 3-year time horizons, respectively. Changing the frequency of follow-up visits, complication rates, and battery replacements had less of an effect on the cost-effectiveness ratios than reducing the cost of ICD placement and leads. LIMITATIONS: The study was limited by the completeness of the data, referral bias, difference in medical therapy between the Duke cohort and the MADIT-II cohort, and not addressing potential upgrades to biventricular devices. CONCLUSIONS: The economic expense of defibrillator implantation in all patients who meet MADIT-II eligibility criteria is substantial. However, in the range of survival benefit observed in MADIT-II, ICD therapy for these patients is economically attractive by conventional standards.

Adult↗

PubMed2005

Structural insights into the interaction and activation of histone deacetylase 3 by nuclear receptor corepressors.

SMRT (silencing mediator of retinoid acid and thyroid hormone receptor) and NCoR (nuclear receptor corepressor) are transcriptional corepressors that play an essential role in the regulation of development and metabolism. This role is achieved, in part, through the recruitment of a key histone deacetylase (HDAC3), which is itself indispensable for cell viability. The assembly of HDAC3 with the deacetylase activation domain (DAD) of SMRT and NCoR is required for activation of the otherwise inert deacetylase. The DAD comprises an N-terminal DAD-specific motif and a C-terminal SANT (SWI3/ADA2/NCoR/TFIIIB)-like domain. We report here the solution structure of the DAD from SMRT, which reveals a four-helical structure. The DAD differs from the SANT (and MYB) domains in that (i) it has an additional N-terminal helix and (ii) there is a notable hydrophobic groove on the surface of the domain. Structure-guided mutagenesis, combined with interaction assays, showed that residues in the vicinity of the hydrophobic groove are required for interaction with (and hence activation of) HDAC3. Importantly, one surface-exposed lysine is required for activation of HDAC3, but not for interaction. This lysine may play a uniquely important role in the mechanism of activating HDAC3.

Amino Acid Sequence↗