3-Dimensional structure of staphylococcal leukocidin and γ-hemolysin

LukF Delineates Conformational Changes Accompanying For-mation of a Transmembrane ChannelLukF Architecture的晶体结构。LukF has the shape of a prolate ellipsoid with dimensions of 72？x34？x25。在LukF的氨基Latch和在干前采用戏剧性不同的表现，当与Hla Protomer的相应区域相比较时。排除这些领域，LukF的折叠是完全固定在Hla制造商的。包含氨基latch （E2-K16） adopt a？strand conformation and extend the inner？sheet of the？-sandwich by one strand in LukF.Measured in terms of solvent accessible surface area， binding amino latch to the LukF core buries 414？^2。在与Hla原型形成对比的情况下，LukF形式的富含糖的区域形成了三条抗阵列的β-表格，它的包装物对抗β-三明治域的内部β-表格。包括七个disordered residues spanning strand 7" and strand 8 （Figures 1 C and 10）， has an ... More a（±）b（±）c（coil）d（±） fold。与β-sandwich域的前干接口中的氢氧化物保留地：有24个van der Walls接口和已埋的表面区域是852 ^2，而靠近670 ^2被Hla氨基锁在绑定在一个类似位点上的不良质子时被Heptamer结构中。干前和氨基贴片之间的直接接触是由包括V13、V17、Y117和F119在内的羟基聚集体调节的。在Hla，一个占领了两个最新位置的居民被预测会在肮脏的传单的国际区域撒谎。Y117和F119之间的juxtaposition of Y117和F119之间的“pre-stem”和“amino latch makes direct”之间的“通信”之间。“在干前β-sheet的表面上面对LukF核心是主要的羟基，而侧面指向溶剂是极的。”就像Hla一样，LukF边缘域包含了大量暴露的芳香族居住地。由W177和R198定位在一个cleft lined是磷脂头部组的绑定站点。在Hla Heptamer，有一个类似的脂质绑定网站，我，W179和R200的Hla驻地和较新的驻地对于将Hla与红细胞膜结合起来至关重要，LukF Monomer和Hla Protomer比较。LukF和Hla原型结构的优越位置重新增强了核心的凝聚力，使其具有非常相似的序列特征，仅为31.7%的成熟多态性。与amino latch and glycine-rich“stem”regions的比较。D. D到第一个接近时，β-sandwich和rim域表现为刚性实体，即在单体（LukF）和heptamer （Hla）中采用不同的相对构象，然后在β sandwich/rim域Juncture中传播了一个小的变化。最近，水溶性LukF-PV单体也分析了3尺寸结构，并发现了与LukF.LukF.LukF.LukF.LukF.LukF.LukF.LukF.LukF.LukF.LukF.LukF.LukF.LukF.LukF.LukF.LukF.LukF.LukF.LukF.LukF.LukF.LukF.LukF.LukF.LukF.LukF.LukF.LukF.LukF.LukF.LukF.LukF.LukF.和Hla原型结构在三角区域的主要适应性之间的主要差异基本差异。在与β-桑德威奇和边缘域有关的修饰性差异性质的对比中，在三角形区域的4个驻地的主要链phi和psi角度中存在较大的差异，这些差异允许LukF前干隐藏在β-桑德威奇域的内部表面上。在Hla原型机中，这些主要链的双向角度差异是>90度，它们与多肽链从原型机核心延伸的三角形结构有关。LukF-干前的使用类似于在寡体毒素中使用的氨基晶格的邻近蛋白质的相同站点，基于Hla Heptamer的模拟。Less（低）

Crystal Structure of LukF Delineates Conformational Changes Accompanying For-mation of a Transmembrane ChannelLukF Architecture. LukF has the shape of a prolate ellipsoid with dimensions of 72Åx34Åx25. In LukF the amino latch and the pre-stem adopt dramatically different conformations when compared to the corresponding regions of an Hla protomer. Excluding these areas, the fold of LukF is identical to the fold of an Hla protomer. The residues that comprise the amino latch (E2-K16) adopt a β-strand conformation and extend the inner β-sheet of the β-sandwich by one strand in LukF.Measured in terms of solvent accessible surface area, binding amino latch to the LukF core buries 414 Å^2. In striking contrast ot the Hla protomer, the glycine-rich region of LukF forms a three-strand antiparalleled β-sheet that packs against the inner β-sheet of the β-sandwich domain. The pre-stem β-sheet, which includes the seven disordered residues spanning strand 7" and strand 8 (Figures 1C and 10), has an … More a(β)b(β)c(coil)d(β) fold. Hydrophobic residues predominate in the pre-stem interface with the β-sandwich domain : there are 24 van der Walls interactions and the buried surface area is 852Å^2, which is close to the 670 Å^2 buried by the Hla amino latch when bound at a similar site on an adjacent protomer in the heptamer structure. Direct contact between the pre-stem and the amino latch is mediated by a cluster of hydrophobic residues that includes V13, V17, Y117, and F119. In Hla, the residues that occupy the latter two positions are predicted to lie at the interfacial region of the lipid bilayer. The juxtaposition of Y117 and F119 between the pre-stem and the amino latch makes direct "communication" between these two key regions possible.LukF Surface Properties and Phospholipid Binding Site. The surface of the pre-stem β-sheet facing the LukF core is primarily hydrophobic while the side directed toward the solvent is polar. Like Hla, the LukF rim domain contains a lot of exposed aromatic residues. Located in a cleft lined by W177 and R198 is a binding site for phospholipid head groups. In the Hla heptamer, there is a similar lipid binding site, i.e., W179 and R200 residues of Hla, and the latter residue is critical for binding of Hla to an erythrocyte membrane.LukF Monomer and Hla Protomer Comparison. Superposition of the LukF and Hla protomer structures reinforces the conclusion that the cores are very similar despite a sequence identity of only 31.7% for the mature polypeptides. The comparison also emphasizes the divergence in conformation at the amino latch and glycine-rich "stem" regions. Fitting of individual domains demonstrated that the r.m.s deviation between Cα positions for the β-sandwich and rim are 2.1 Å and 2.4 Å, respectively. To a first approximation, the β-sandwich and rim domains behave as rigid bodies that adopt different relative conformations in the monomer (LukF) and heptamer (Hla) due to small changes spread over a number of residues at the β sandwich/rim domain juncture. Recently, the 3-dimensional structure of the water-soluble LukF-PV monomer also analysed and was found to be basically similar to that of LukF.Major conformational differences between LukF and the Hla protomer structures occur in the triangle region. In contrast to the diffuse nature of the conformational differences relating the β- sandwich and rim domains, there are larger differences in main chain phi and psi angles for 4 residues in the triangle region which allow the LukF pre-stem to fold against the inner surface of the β-sandwich domain. In the Hla protomer, these main chain dihedral angles differ by>90゜ and are associated with a triangle conformation in which the polypeptide chain extends from the protomer core. The LukF pre-stem occupies approximately the same site that the amino latch of a neighboring protomer occupies in the oligomeric toxin, based on the analogy with the Hla heptamer. Less