Crystal structure of three consecutive laminin-type epidermal growth factor-like (LE) modules of laminin gamma1 chain harboring the nidogen binding site.
Crystal structure of three consecutive laminin-type epidermal growth factor-like (LE) modules of laminin gamma1 chain harboring the nidogen binding site.
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含有巢蛋白结合位点的层粘连蛋白 gamma1 链的三个连续层粘连蛋白型表皮生长因子样 (LE) 模块的晶体结构。
DOI：
10.1006/jmbi.1996.0191
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发表时间：
1996
影响因子：
5.6
通讯作者：
R. Huber
中科院分区：
文献类型：
--
作者：
J. Stetefeld;U. Mayer;R. Timpl;R. Huber
小鼠层粘连蛋白γ 1链的三个连续层粘连蛋白型EGF样（LE）模块γ 1 III 3 -5（位置738至899）的结构已通过空间群为p6（4）22（a=B=74.57埃，c = 185.11埃和γ = 120度）的晶体中的多个同晶置换确定。使用限制晶体学精修将晶体结构精修至19.72%的R因子，对于14，983个独立反射，在2.1埃分辨率下强度F（obs）> 0，与理想键长和键角的均方根偏差分别为0.012埃和1.690度。最终的模型由162个残基内的1179个（非氢）蛋白质原子和119个水分子组成。该分子显示出约76埃长的棒状结构，其中各个模块相对于彼此扭曲约70度。每个模块具有相同的二硫键连接Cys 1-Cys 3（环a）、Cys 2-Cys 4（环B）、Cys 5-Cys 6（环c）和Cys 7-Cys 8（环d），前三个与表皮生长因子（EGF）相同。所有三个LE模块都显示出很少的二级结构，主要限于环d，但它们在结构的其他几个细节上有所不同。LE模块之间的界面接触基于前一模块的环d的疏水核心与后一模块的环B中的第一个半胱氨酸和暴露残基之间的氢键和疏水相互作用。先前显示模块4贡献了椎板的主要巢蛋白结合位点，并且定点诱变证明了Asp 800、Asn 802、Val 804和Tyr 819在环a和c中的特异性结合作用。这四个残基的侧链均以线性阵列位于表面上，Tyr 819和Val 804之间相距17埃。整个巢蛋白结合位点通过主链氢键稳定化，所述主链氢键部分源自环B和c之间的连接（残基Leu 815和Lys 816）。这些数据表明LE模块的独特性质，与EGF的相似性很小。它们还表明，结合环中的关键残基提供了与巢蛋白的直接接触，并解释了环a和c之间的协同作用，这对结合至关重要。
The structure of three consecutive laminin-type EGF-like (LE) modules of mouse laminin gammma1 chain, gamma1III3-5 (positions 738 to 899), has been determined by multiple isomorphous replacement in a crystal of space group p6(4)22 (a=b=74.57 angstroms, c = 185.11 angstroms and gamma = 120 degrees). The crystal structure was refined using restrained crystallographic refinement to an R-factor of 19.72% for 14,983 independent reflections with intensities F(obs)> 0 at 2.1 angstroms resolution, with root mean square deviation of 0.012 angstroms and 1.690 degrees from ideal bond lengths and bond angles, respectively. The final model consisted of 1179 (non-hydrogen) protein atoms within 162 residues and 119 water molecules. The molecule showed a rod-like structure of about 76 angstroms length with individual modules twisted relative to each other by about 70 degrees. Each module has the same disulfide bond connections Cys1-Cys3 (loop a), Cys2-Cys4 (loop b), Cys5-Cys6 (loop c) and Cys7-Cys8 (loop d), the first three being identical to epidermal growth factor (EGF). All three LE modules showed little secondary structure which was mainly restricted to loop d, but they differed in several other details of their structure. The interface contacts between the LE modules are based on hydrogen bonds and hydrophobic interactions between the hydrophobic core of loop d of the preceding module and the first cysteine and an exposed residue in loop b of the following module. Module 4 was previously shown to contribute the major nidogen binding site of laminis and site-directed mutagenesis demonstrated a specific binding role for Asp800, Asn802, Val804 and Tyr819 in loops a and c. The side-chain of these four residues are all located on the surface in a linear array and separated by a distance of 17 angstroms between Tyr819 and Val804. The entire nidogen binding site is stabilized via main-chain hydrogen bonds which are in part derived from the link between loops b and c (residues Leu815 and Lys816). The data demonstrate the unique nature of the LE modules and only a remote similarity to EGF. They also indicate that the crucial residues in the binding loops provide direct contacts with nidogen and explain the synergism between loops a and c which is essential for binding.
鼠表皮生长因子的溶液结构：通过核磁共振和距离几何测定多肽主链折叠。
DOI：
10.1073/pnas.84.15.5226
发表时间：
1987
影响因子：
11.1
作者：
Montelione,GT;Wüthrich,K;Nice,EC;Burgess,AW;Scheraga,HA
通讯作者：
Scheraga,HA
影响因子：
11.4
作者：
FOX, JW;MAYER, U;CHU, ML
通讯作者：
CHU, ML
影响因子：
2.7
作者：
Dong, Qiang;Yuan, Guoqiang;Pan, Yawen
通讯作者：
Pan, Yawen