來自貝勒醫(yī)學(xué)院生物化學(xué)與分子生物學(xué)系的研究人員發(fā)現(xiàn)并證明了人端粒結(jié)合因子TRF2如何在不同信號(hào)途徑中完成調(diào)控作用的機(jī)制，這對(duì)于進(jìn)一步了解端粒作用,，以及端粒和不同信號(hào)途徑之間的關(guān)系具有重要的意義,。這一研究成果公布在Nature子刊Nature Structural & Molecular Biology雜志上。
哺乳動(dòng)物細(xì)胞中,，端粒結(jié)合因子（telomere repeat binding factor,TRF)在端粒酶陽性和陰性細(xì)胞中的定位以及在細(xì)胞周期中的表達(dá)中扮演著重要的角色,。其中端粒DNA結(jié)合蛋白TRF2(TTAGGG repeat binding factor-2)以二聚體形式通過Myb結(jié)構(gòu)域與端粒重復(fù)序列TTAGGG結(jié)合，并與TRF1,、TIN2,、Rap1、TINT1及POT1蛋白組成Shelterin蛋白復(fù)合物,，協(xié)同在端粒動(dòng)態(tài)平衡維持過程中起關(guān)鍵作用,，進(jìn)而影響整個(gè)基因組的穩(wěn)定性。此外,，TRF2在細(xì)胞DNA損傷應(yīng)答過程中可能發(fā)揮重要作用,。
但是迄今為止，科學(xué)家們還不了解TRF2與不同信號(hào)途徑相互作用的機(jī)制,，在這篇文章中,，研究人員利用定向多肽文庫，證明人類TRF2的TRFH（TRF同源異形)結(jié)構(gòu)域能識(shí)別[Y/F]XL多肽（YYHKYRLSPL）,，干擾TRF2 TRFH結(jié)構(gòu)域與靶標(biāo)之間的相互作用還會(huì)導(dǎo)致端粒DNA損傷修復(fù),。這些研究結(jié)果都說明TRF2分子能作為一種蛋白中心，通過聚集不同的信號(hào)分子調(diào)控端粒,。（生物谷Bioon.com）
Nature：研究揭示端粒酶關(guān)鍵部位三維結(jié)構(gòu)
Nature：端粒復(fù)合體TBPb的人類同源結(jié)構(gòu)被發(fā)現(xiàn)
生物谷推薦原始出處：
Nature Structural & Molecular Biology 16, 372 - 379 (2009) 15 March 2009 | doi:10.1038/nsmb.1575
TRF2 functions as a protein hub and regulates telomere maintenance by recognizing specific peptide motifs
Hyeung Kim1,3, Ok-Hee Lee1,3, Huawei Xin1,3, Liuh-Yow Chen1, Jun Qin1, Heekyung Kate Chae1, Shiaw-Yih Lin2, Amin Safari1, Dan Liu1 & Zhou Songyang1
In mammalian cells, the telomeric repeat binding factor (TRF) homology (TRFH) domain–containing telomeric proteins TRF1 and TRF2 associate with a collection of molecules necessary for telomere maintenance and cell-cycle progression. However, the specificity and the mechanisms by which TRF2 communicates with different signaling pathways remain largely unknown. Using oriented peptide libraries, we demonstrate that the TRFH domain of human TRF2 recognizes [Y/F]XL peptides with the consensus motif YYHKYRLSPL. Disrupting the interactions between the TRF2 TRFH domain and its targets resulted in telomeric DNA-damage responses. Furthermore, our genome-wide target analysis revealed phosphatase nuclear targeting subunit (PNUTS) and microcephalin 1 (MCPH1) as previously unreported telomere-associated proteins that directly interact with TRF2 via the [Y/F]XL motif. PNUTS and MCPH1 can regulate telomere length and the telomeric DNA-damage response, respectively. Our findings indicate that an array of TRF2 molecules functions as a protein hub and regulates telomeres by recruiting different signaling molecules via a linear sequence code.
1 Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
2 Department of System Biology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77054, USA.
3 These authors contributed equally to this work.
