Bohley P
Physiologisch-chemisches Institut der Universität, Tübingen, Germany.
Biol Chem. 1996 Jul-Aug;377(7-8):425-35.
Cellular proteins turn over with rates varying more than 1000 fold and all organelles are involved in this process of renewal. Although the surface of protein molecules bears many peptide bonds, which could be potential cleavage sites for proteases, only a small fraction of all cellular proteins is subject to very rapid turnover, with half-lives of less than one hour in mammalian cells. Many of these proteins play key roles in basic regulatory mechanisms. One of the features that make proteins short-lived is surface hydrophobicity which is increased in nascent polypeptide chains before association with chaperones, in oligomeric proteins before the association of the monomers, and in many enzymes in absence of their substrates. Cellular proteases tend to act most rapidly on peptide bonds involving (or near to) apolar amino acids. A striking correlation has been found between the half-lives of cellular proteins and their surface hydrophobicity. Clusters of hydrophobic residues appear to be necessary for ubiquitination. Apolar amino acid residues that are hidden can be exposed after oxidation of proteins or after binding of ubiquitin molecules. Additionally, tetraubiquitin exposes many hydrophobic residues which are essential for targeting of the ubiquitinated substrate proteins to a 50 kDa-subunit of the 26S-protease.
细胞蛋白质的更新速率差异超过1000倍，所有细胞器都参与这一更新过程。尽管蛋白质分子表面有许多肽键，可能成为蛋白酶的潜在切割位点，但在所有细胞蛋白质中，只有一小部分更新速度非常快，在哺乳动物细胞中的半衰期不到一小时。其中许多蛋白质在基本调节机制中发挥关键作用。使蛋白质寿命短暂的一个特征是表面疏水性，在新生多肽链与伴侣蛋白结合之前、寡聚蛋白中单体结合之前以及许多酶在没有底物时，表面疏水性都会增加。细胞蛋白酶倾向于对涉及（或靠近）非极性氨基酸的肽键作用最快。已发现细胞蛋白质的半衰期与其表面疏水性之间存在显著相关性。疏水残基簇似乎是泛素化所必需的。隐藏的非极性氨基酸残基在蛋白质氧化后或泛素分子结合后可能会暴露出来。此外，四聚泛素会暴露许多疏水残基，这些残基对于将泛素化的底物蛋白靶向26S蛋白酶的50 kDa亚基至关重要。
