Adamian L, Liang J
Department of Bioengineering, University of Illinois at Chicago, 851 S. Morgan Street RM 218, MC-063, Chicago, IL 60607, USA.
J Mol Biol. 2001 Aug 24;311(4):891-907. doi: 10.1006/jmbi.2001.4908.
Helix-helix packing plays a critical role in maintaining the tertiary structures of helical membrane proteins. By examining the overall distribution of voids and pockets in the transmembrane (TM) regions of helical membrane proteins, we found that bacteriorhodopsin and halorhodopsin are the most tightly packed, whereas mechanosensitive channel is the least tightly packed. Large residues F, W, and H have the highest propensity to be in a TM void or a pocket, whereas small residues such as S, G, A, and T are least likely to be found in a void or a pocket. The coordination number for non-bonded interactions for each of the residue types is found to correlate with the size of the residue. To assess specific interhelical interactions between residues, we have developed a new computational method to characterize nearest neighboring atoms that are in physical contact. Using an atom-based probabilistic model, we estimate the membrane helical interfacial pairwise (MHIP) propensity. We found that there are many residue pairs that have high propensity for interhelical interactions, but disulfide bonds are rarely found in the TM regions. The high propensity pairs include residue pairs between an aromatic residue and a basic residue (W-R, W-H, and Y-K). In addition, many residue pairs have high propensity to form interhelical polar-polar atomic contacts, for example, residue pairs between two ionizable residues, between one ionizable residue and one N or Q. Soluble proteins do not share this pattern of diverse polar-polar interhelical interaction. Exploratory analysis by clustering of the MHIP values suggests that residues similar in side-chain branchness, cyclic structures, and size tend to have correlated behavior in participating interhelical interactions. A chi-square test rejects the null hypothesis that membrane protein and soluble protein have the same distribution of interhelical pairwise propensity. This observation may help us to understand the folding mechanism of membrane proteins.
螺旋-螺旋堆积在维持螺旋膜蛋白的三级结构中起着关键作用。通过研究螺旋膜蛋白跨膜（TM）区域中空隙和口袋的整体分布，我们发现细菌视紫红质和嗜盐视紫红质堆积最紧密，而机械敏感通道堆积最松散。大残基F、W和H最倾向于处于TM空隙或口袋中，而小残基如S、G、A和T最不可能出现在空隙或口袋中。发现每种残基类型的非键相互作用配位数与残基大小相关。为了评估残基之间特定的螺旋间相互作用，我们开发了一种新的计算方法来表征物理接触的最近邻原子。使用基于原子的概率模型，我们估计膜螺旋界面成对（MHIP）倾向。我们发现有许多残基对具有高螺旋间相互作用倾向，但在TM区域很少发现二硫键。高倾向对包括芳香族残基和碱性残基之间的残基对（W-R、W-H和Y-K）。此外，许多残基对有高倾向形成螺旋间极性-极性原子接触，例如，两个可电离残基之间、一个可电离残基与一个N或Q之间的残基对。可溶性蛋白不具有这种多样的极性-极性螺旋间相互作用模式。通过对MHIP值进行聚类的探索性分析表明，在侧链分支、环状结构和大小方面相似的残基在参与螺旋间相互作用时往往具有相关行为。卡方检验拒绝了膜蛋白和可溶性蛋白具有相同螺旋间成对倾向分布的零假设。这一观察结果可能有助于我们理解膜蛋白的折叠机制。
