Russo Santina, Baumann Ulrich
Departement für Chemie und Biochemie, University of Berne, Freiestrasse 3, CH-3012 Bern, Switzerland.
J Biol Chem. 2004 Dec 3;279(49):51275-81. doi: 10.1074/jbc.M409455200. Epub 2004 Sep 16.
Protein turnover is an essential process in living cells. The degradation of cytosolic polypeptides is mainly carried out by the proteasome, resulting in 7-9-amino acid long peptides. Further degradation is usually carried out by energy-independent proteases like the tricorn protease from Thermoplasma acidophilum. Recently, a novel tetrahedral-shaped dodecameric 480-kDa aminopeptidase complex (TET) has been described in Haloarcula marismortui that differs from the known ring- or barrel-shaped self-compartmentalizing proteases. This complex is capable of degrading most peptides down to amino acids. We present here the crystal structure of the tetrahedral aminopeptidase homolog FrvX from Pyrococcus horikoshii. The monomer has a typical clan MH fold, as found for example in Aeromonas proteolytica aminopeptidase, containing a dinuclear zinc active center. The quaternary structure is built by dimers with a length of 100 A that form the edges of the tetrahedron. All 12 active sites are located on the inside of the tetrahedron. Substrate access is granted by pores with a maximal diameter of 10 A, allowing only small peptides and unfolded proteins access to the active site.
蛋白质周转是活细胞中的一个基本过程。胞质多肽的降解主要由蛋白酶体进行，产生7 - 9个氨基酸长的肽段。进一步的降解通常由不依赖能量的蛋白酶进行，如嗜热栖热菌的三角蛋白酶。最近，在死海嗜盐菌中发现了一种新型的四面体形状的十二聚体480 kDa氨肽酶复合物（TET），它不同于已知的环状或桶状自分隔蛋白酶。这种复合物能够将大多数肽段降解为氨基酸。我们在此展示了来自嗜热栖热放线菌的四面体氨肽酶同源物FrvX的晶体结构。单体具有典型的MH家族折叠，例如在解蛋白气单胞菌氨肽酶中发现的那样，包含一个双核锌活性中心。四级结构由长度为100 Å的二聚体构建而成，这些二聚体形成四面体的边缘。所有12个活性位点都位于四面体内部。底物通过最大直径为10 Å的孔进入，仅允许小肽和未折叠的蛋白质进入活性位点。
