The X-Ray Crystal Structure of the Keratin 1-Keratin 10 Helix 2B Heterodimer Reveals Molecular Surface Properties and Biochemical Insights into Human Skin Disease.
The X-Ray Crystal Structure of the Keratin 1-Keratin 10 Helix 2B Heterodimer Reveals Molecular Surface Properties and Biochemical Insights into Human Skin Disease.
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角蛋白1-克拉素10螺旋2B异二聚体的X射线晶体结构揭示了分子表面特性和对人皮肤病的生化见解。
DOI：
10.1016/j.jid.2016.08.018
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发表时间：
2017-01
期刊：
影响因子：
--
通讯作者：
Milstone LM
中科院分区：
文献类型：
--
作者：
Bunick CG;Milstone LM
角蛋白1（K1）和10（K10）是在分化的表皮中表达的初级角蛋白。K1/K10突变与人类皮肤病有关。我们确定了K1和K10的远端（2B）螺旋之间的复合物的晶体结构，以更好地了解人类角蛋白结构与功能的关系。3.3纳米分辨率的结构证实了以前生化分析推断的许多特征，但增加了新的，意想不到的见解。它证明了一个平行的卷曲螺旋异二聚体，具有主要疏水的分子间界面;该异二聚体通过Cys 401 K10二硫键与第二个K1-K10-2B异二聚体形成了更高阶的复合物，尽管键角是意料之外的。K1-K10-2B的分子表面分析鉴定了几个口袋，一个邻近二硫键并且在K5-K14中保守。K1-K10结构的溶剂可及表面积为20-25%疏水性。2B区近端（N-末端）含有混合酸性和碱性斑块，而远端（C-末端）主要为酸性。将K1-K10和K5-K14之间的保守和非保守残基定位到结构上，表明大多数独特残基沿外螺旋脊沿着。最后，该结构允许对表型皮肤病患者中发现的K1/K10错义突变引起的有害影响进行新的分析。
Keratins 1 (K1) and 10 (K10) are the primary keratins expressed in differentiated epidermis. Mutations in K1/K10 are associated with human skin diseases. We determined the crystal structure of the complex between the distal (2B) helices of K1 and K10 to better understand how human keratin structure correlates with function. The 3.3Å resolution structure confirms many features inferred by previous biochemical analyses but adds new, unexpected insights. It demonstrates a parallel, coiled-coil heterodimer with a predominantly hydrophobic intermolecular interface; this heterodimer formed a higher order complex with a second K1-K10-2B heterodimer via a Cys401K10 disulfide link, although the bond angle is unanticipated. Molecular surface analysis of K1-K10-2B identified several pockets, one adjacent to the disulfide linkage and conserved in K5-K14. The solvent accessible surface area of the K1-K10 structure is 20-25% hydrophobic. The 2B region contains mixed acidic and basic patches proximally (N-terminal) whereas it is largely acidic distally (C-terminal). Mapping of conserved and non-conserved residues between K1-K10 and K5-K14 onto the structure demonstrated the majority of unique residues align along the outer helical ridge. Finally, the structure permitted a fresh analysis of the deleterious effects caused by K1/K10 missense mutations found in patients with phenotypic skin disease.
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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：
Cowtan, K
DOI：
10.1016/0141-8130(89)90020-2
发表时间：
1989-10-01
影响因子：
8.2
作者：
WOODS, EF
通讯作者：
WOODS, EF
影响因子：
16.8
作者：
Lee, Chang-Hun;Kim, Min-Sung;Chung, Byung Min;Leahy, Daniel J.;Coulombe, Pierre A.
通讯作者：
Coulombe, Pierre A.
影响因子：
15.9
作者：
SYDER, AJ;YU, QC;FUCHS, E
通讯作者：
FUCHS, E
影响因子：
4.6
作者：
Matsuba, S;Suga, Y;Ogawa, H
通讯作者：
Ogawa, H