Kleiger Gary, Grothe Robert, Mallick Parag, Eisenberg David
Howard Hughes Medical Institute, UCLA-DOE Laboratory of Structural Biology and Molecular Medicine, Molecular Biology Institute, University of California at Los Angeles, P.O. Box 951570, Los Angeles, California 90095-1570, USA.
Biochemistry. 2002 May 14;41(19):5990-7. doi: 10.1021/bi0200763.
The GXXXG motif is a frequently occurring sequence of residues that is known to favor helix-helix interactions in membrane proteins. Here we show that the GXXXG motif is also prevalent in soluble proteins whose structures have been determined. Some 152 proteins from a non-redundant PDB set contain at least one alpha-helix with the GXXXG motif, 41 +/- 9% more than expected if glycine residues were uniformly distributed in those alpha-helices. More than 50% of the GXXXG-containing alpha-helices participate in helix-helix interactions. In fact, 26 of those helix-helix interactions are structurally similar to the helix-helix interaction of the glycophorin A dimer, where two transmembrane helices associate to form a dimer stabilized by the GXXXG motif. As for the glycophorin A structure, we find backbone-to-backbone atomic contacts of the C alpha-H...O type in each of these 26 helix-helix interactions that display the stereochemical hallmarks of hydrogen bond formation. These glycophorin A-like helix-helix interactions are enriched in the general set of helix-helix interactions containing the GXXXG motif, suggesting that the inferred C alpha-H...O hydrogen bonds stabilize the helix-helix interactions. In addition to the GXXXG motif, some 808 proteins from the non-redundant PDB set contain at least one alpha-helix with the AXXXA motif (30 +/- 3% greater than expected). Both the GXXXG and AXXXA motifs occur frequently in predicted alpha-helices from 24 fully sequenced genomes. Occurrence of the AXXXA motif is enhanced to a greater extent in thermophiles than in mesophiles, suggesting that helical interaction based on the AXXXA motif may be a common mechanism of thermostability in protein structures. We conclude that the GXXXG sequence motif stabilizes helix-helix interactions in proteins, and that the AXXXA sequence motif also stabilizes the folded state of proteins.
GXXXG基序是一种常见的残基序列，已知它有利于膜蛋白中的螺旋 - 螺旋相互作用。在此我们表明，GXXXG基序在已确定结构的可溶性蛋白中也很普遍。来自非冗余蛋白质数据库（PDB）集合的约152种蛋白质含有至少一个带有GXXXG基序的α螺旋，比在这些α螺旋中甘氨酸残基均匀分布时预期的数量多41±9％。超过50％的含有GXXXG的α螺旋参与螺旋 - 螺旋相互作用。事实上，其中26种螺旋 - 螺旋相互作用在结构上类似于血型糖蛋白A二聚体的螺旋 - 螺旋相互作用，其中两个跨膜螺旋缔合形成由GXXXG基序稳定的二聚体。至于血型糖蛋白A的结构，我们在这26种螺旋 - 螺旋相互作用的每一种中都发现了Cα - H...O型的主链 - 主链原子接触，这些接触展现出氢键形成的立体化学特征。这些类似血型糖蛋白A的螺旋 - 螺旋相互作用在包含GXXXG基序的螺旋 - 螺旋相互作用的总体集合中富集，这表明推断的Cα - H...O氢键稳定了螺旋 - 螺旋相互作用。除了GXXXG基序外，来自非冗余PDB集合的约808种蛋白质含有至少一个带有AXXXA基序的α螺旋（比预期多30±3％）。GXXXG和AXXXA基序在来自24个全序列基因组的预测α螺旋中都频繁出现。嗜热菌中AXXXA基序的出现比嗜温菌中增强的程度更大，这表明基于AXXXA基序的螺旋相互作用可能是蛋白质结构中热稳定性的一种常见机制。我们得出结论，GXXXG序列基序稳定蛋白质中的螺旋 - 螺旋相互作用，并且AXXXA序列基序也稳定蛋白质的折叠状态。
