Identification of bZIP interaction partners of viral proteins HBZ, MEQ, BZLF1, and K-bZIP using coiled-coil arrays.
Identification of bZIP interaction partners of viral proteins HBZ, MEQ, BZLF1, and K-bZIP using coiled-coil arrays.
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DOI：
10.1021/bi902065k
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发表时间：
2010-03-09
期刊：
影响因子：
2.9
通讯作者：
Keating, Amy E.
中科院分区：
文献类型：
--
作者：
Reinke, Aaron W.;Grigoryan, Gevorg;Keating, Amy E.
碱性区亮氨酸拉链转录因子（bZIPs）含有一个富含碱性氨基酸的片段，可以结合DNA，随后是一个亮氨酸拉链，可以与其他亮氨酸拉链相互作用，形成卷曲螺旋同源或异源二聚体。几种病毒编码含有bZIP结构域的蛋白质，包括四种编码与任何人类蛋白质缺乏显著同源性的bZIP。我们研究了这四种病毒bZIPs的相互作用特异性，通过使用卷曲螺旋阵列评估自我协会以及与33个代表性的人类bZIPs的异源相互作用。这些阵列概括了报告的病毒与人类的相互作用，并发现了新的关联。MEQ和HBZ与多个人类伴侣相互作用，与任何人类bZIP相比具有独特的相互作用谱，而K-bZIP和BZLF 1显示同源特异性。检测到的新相互作用包括HBZ与MAFB、MAFG、ATF 2、CEBPG和CREBZF以及MEQ与NFIL 3。这些都证实了在溶液中使用圆二色性。在MARE位点DNA存在下，HBZ可以与MAFB和MAFG异源结合，这种相互作用依赖于HBZ的碱性区域。NFIL 3和MEQ具有不同但重叠的DNA结合特异性，并且可以与DNA形成异源复合物。使用考虑对MEQ的亲和力和相对于其他不期望的bZIP型相互作用的特异性的计算设计来产生MEQ二聚化抑制剂。这种肽，抗MEQ，结合MEQ稳定和特异性，如使用卷曲螺旋阵列和圆二色性在溶液中测定。抗MEQ还抑制MEQ与DNA的结合。这些研究可以指导病毒和人类bZIP复合物的功能的进一步调查。
Basic-region leucine-zipper transcription factors (bZIPs) contain a segment rich in basic amino acids that can bind DNA, followed by a leucine zipper that can interact with other leucine zippers to form coiled-coil homo- or heterodimers. Several viruses encode proteins containing bZIP domains, including four that encode bZIPs lacking significant homology to any human protein. We investigated the interaction specificity of these four viral bZIPs by using coiled-coil arrays to assess self-associations as well as hetero-interactions with 33 representative human bZIPs. The arrays recapitulated reported viral-human interactions and also uncovered new associations. MEQ and HBZ interacted with multiple human partners and had unique interaction profiles compared to any human bZIPs, whereas K-bZIP and BZLF1 displayed homo-specificity. New interactions detected included HBZ with MAFB, MAFG, ATF2, CEBPG, and CREBZF, and MEQ with NFIL3. These were confirmed in solution using circular dichroism. HBZ can hetero-associate with MAFB and MAFG in the presence of MARE-site DNA, and this interaction is dependent on the basic region of HBZ. NFIL3 and MEQ have different yet overlapping DNA-binding specificities and can form a heterocomplex with DNA. Computational design considering both affinity for MEQ and specificity with respect to other undesired bZIP-type interactions was used to generate a MEQ dimerization inhibitor. This peptide, anti-MEQ, bound MEQ both stably and specifically, as assayed using coiled-coil arrays and circular dichroism in solution. Anti-MEQ also inhibited MEQ binding to DNA. These studies can guide further investigation of the function of viral and human bZIP complexes.
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影响因子：
8
作者：
Daury, L;Busson, M;Cabello, G
通讯作者：
Cabello, G
DOI：
10.1073/pnas.141090998
发表时间：
2001-07-03
影响因子：
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作者：
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影响因子：
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影响因子：
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作者：
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Robertson, D. L.
DOI：
10.1073/pnas.88.9.3720
发表时间：
1991-05-01
影响因子：
11.1
作者：
HAI, T;CURRAN, T
通讯作者：
CURRAN, T