Crystal structure of the HEAT domain from the Pre-mRNA processing factor Symplekin.
Crystal structure of the HEAT domain from the Pre-mRNA processing factor Symplekin.
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DOI：
10.1016/j.jmb.2009.06.062
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发表时间：
2009-09-11
影响因子：
5.6
通讯作者：
Redinbo, Matthew R.
中科院分区：
文献类型：
--
作者：
Kennedy, Sarah A.;Frazier, Monica L.;Steiniger, Mindy;Mast, Ann M.;Marzluff, William F.;Redinbo, Matthew R.
虽然在后生动物中，依赖复制的组蛋白mRNAs是通过3‘端切割而不是多腺化来处理的，但大多数真核生物的前mRNAs是通过3’端切割和多聚腺化来处理的。负责处理规范和组蛋白前体mRNAs的大分子复合体含有~1,160个残基的蛋白Symplekin。二级结构预测算法在所有已知序列的Symplekins的300个N-末端残基中识别出可能的热域。研究了该结构域的结构和动力学，以开始阐明Symplekin在mRNA成熟中所起的作用。用SAD相位法测定了果蝇黑腹果蝇Symplekin热区的晶体结构，其分辨率为2.4？该结构显示出5个典型的热重复序列以及在第四和第五个重复序列之间延伸的31个氨基酸环(环8)，该环在密切相关的Symplekin序列中保守。分子动力学模拟表明，环8的存在抑制了热域的相关和反相关运动，从而为潜在的蛋白质-蛋白质相互作用提供了一个中性表面。热区通常用于这种大分子接触。Symplekin热区不仅在结构上与几个已建立的支架蛋白相一致，而且据报道还与调节3‘-端加工所必需的蛋白质相联系。综上所述，这些数据支持这样的结论，即Symplekin热域是蛋白质相互作用的支架，对mRNA成熟过程至关重要。
The majority of eukaryotic pre-mRNAs are processed by 3′-end cleavage and polyadenylation, although in metazoa the replication-dependant histone mRNAs are processed by 3′-end cleavage but not polyadenylation. The macromolecular complex responsible for processing both canonical and histone pre-mRNAs contains the ~1,160-residue protein Symplekin. Secondary structural prediction algorithms identified putative HEAT domains in the 300 N-terminal residues of all Symplekins of known sequence. The structure and dynamics of this domain were investigated to begin elucidating the role Symplekin plays in mRNA maturation. The crystal structure of the Drosophila melanogaster Symplekin HEAT domain was determined to 2.4 Å resolution using SAD phasing methods. The structure exhibits 5 canonical HEAT repeats along with an extended 31 amino acid loop (loop 8) between the fourth and fifth repeat that is conserved within closely related Symplekin sequences. Molecular dynamics simulations of this domain show that the presence of loop 8 dampens correlated and anticorrelated motion in the HEAT domain, therefore providing a neutral surface for potential protein-protein interactions. HEAT domains are often employed for such macromolecular contacts. The Symplekin HEAT region not only structurally aligns with several established scaffolding proteins, but also has been reported to contact proteins essential for regulating 3′-end processing. Taken together, these data support the conclusion that the Symplekin HEAT domain serves as a scaffold for protein-protein interactions essential to the mRNA maturation process.
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Pfam：氏族、网络工具和服务。
影响因子：
14.9
作者：
Finn, Robert D.;Mistry, Jaina;Schuster-Bockler, Benjamin;Griffiths-Jones, Sam;Hollich, Volker;Lassmann, Timo;Moxon, Simon;Marshall, Mhairi;Khanna, Ajay;Durbin, Richard;Eddy, Sean R.;Sonnhammer, Erik L. L.;Bateman, Alex
通讯作者：
Bateman, Alex
影响因子：
2.9
作者：
Balbo, PB;Meinke, G;Bohm, A
通讯作者：
Bohm, A
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
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影响因子：
64.8
作者：
Cho, Uhn Soo;Xu, Wenqing
通讯作者：
Xu, Wenqing
影响因子：
5.8
作者：
Cuff, JA;Clamp, ME;Barton, GJ
通讯作者：
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