Department of Chemical and Structural Biology, Weizmann Institute of Science, Rehovot 7610001, Israel.
Biomolecules. 2023 Feb 15;13(2):363. doi: 10.3390/biom13020363.
Many proteins have intrinsically disordered regions (IDRs), which are often characterized by a high fraction of charged residues with polyampholytic (i.e., mixed charge) or polyelectrolytic (i.e., uniform charge) characteristics. Polyelectrolytic IDRs include consecutive positively charged Lys or Arg residues (K/R repeats) or consecutive negatively charged Asp or Glu residues (D/E repeats). In previous research, D/E repeats were found to be about five times longer than K/R repeats and to be much more common in eukaryotes. Within these repeats, a preference is often observed for E over D and for K over R. To understand the greater prevalence of D/E over K/R repeats and the higher abundance of E and K, we simulated the conformational ensemble of charged homo-polypeptides (polyK, polyR, polyD, and polyE) using molecular dynamics simulations. The conformational preferences and dynamics of these polyelectrolytic polypeptides change with changes in salt concentration. In particular, polyD and polyE are more sensitive to salt than polyK and polyR, as polyD and polyE tend to adsorb more divalent cations, which leads to their having more compact conformations. We conclude with a discussion of biophysical explanations for the relative abundance of charged amino acids and particularly for the greater abundance of D/E repeats over K/R repeats.
许多蛋白质都具有内源性无序区域（IDR），其通常具有较高比例的带电荷残基，这些残基具有聚电解质（即混合电荷）或多阴离子（即均匀电荷）特性。聚电解质 IDR 包括连续的正电荷 Lys 或 Arg 残基（K/R 重复）或连续的负电荷 Asp 或 Glu 残基（D/E 重复）。在之前的研究中，D/E 重复比 K/R 重复长约五倍，并且在真核生物中更为常见。在这些重复中，通常观察到 E 对 D 的偏好以及 K 对 R 的偏好。为了理解 D/E 重复比 K/R 重复更为普遍，以及 E 和 K 更为丰富的原因，我们使用分子动力学模拟模拟了带电同聚物（polyK、polyR、polyD 和 polyE）的构象集合。这些聚电解质多肽的构象偏好和动力学随盐浓度的变化而变化。特别是，polyD 和 polyE 比 polyK 和 polyR 对盐更敏感，因为 polyD 和 polyE 往往会吸附更多的二价阳离子，从而导致它们具有更紧凑的构象。最后，我们讨论了带电氨基酸相对丰度的生物物理解释，特别是 D/E 重复比 K/R 重复更为丰富的原因。
