Goethe University Frankfurt, Medical School, Institute of Biochemistry II, Structural Bioenergetics Group, Max-von-Laue Str. 9, 60438 Frankfurt, Germany.
Goethe University Frankfurt, Institute of Pharmaceutical Chemistry, Max-von-Laue Str. 9, 60438 Frankfurt, Germany.
Biochim Biophys Acta Mol Cell Res. 2017 Oct;1864(10):1913-1920. doi: 10.1016/j.bbamcr.2017.08.006. Epub 2017 Aug 9.
The mitochondrial acyl carrier protein (ACPM/NDUFAB1) is a central element of the mitochondrial fatty acid synthesis type II machinery. Originally ACPM was detected as a subunit of respiratory complex I but the reason for the association with the large enzyme complex remained elusive. Complex I from the aerobic yeast Yarrowia lipolytica comprises two different ACPMs, ACPM1 and ACPM2. They are anchored to the protein complex by LYR (leucine-tyrosine-arginine) motif containing protein (LYRM) subunits LYRM3 (NDUFB9) and LYRM6 (NDUFA6). The ACPM1-LYRM6 and ACPM2-LYRM3 modules are essential for complex I activity and assembly/stability, respectively. We show that in addition to the complex I bound fraction, ACPM1 is present as a free matrix protein and in complex with the soluble LYRM4(ISD11)/NFS1 complex implicated in Fe-S cluster biogenesis. We show that the presence of a long acyl chain bound to the phosphopantetheine cofactor is important for docking ACPMs to protein complexes and we propose that association of ACPMs and LYRMs is universally based on a new protein-protein interaction motif.
线粒体酰基辅酶 A 载体蛋白 (ACPM/NDUFAB1) 是线粒体脂肪酸合成 II 型机器的核心元件。最初，ACPM 被检测为呼吸复合物 I 的一个亚基，但与大型酶复合物的关联原因仍不清楚。需氧酵母解脂耶氏酵母的复合物 I 由两种不同的 ACPM 组成，即 ACPM1 和 ACPM2。它们通过含有亮氨酸-酪氨酸-精氨酸 (LYR) 基序的蛋白 (LYRM) 亚基 LYRM3 (NDUFB9) 和 LYRM6 (NDUFA6) 锚定在蛋白复合物上。ACPM1-LYRM6 和 ACPM2-LYRM3 模块分别对复合物 I 的活性和组装/稳定性至关重要。我们表明，除了与复合物 I 结合的部分外，ACPM1 还作为游离基质蛋白存在，并与可溶性 LYRM4(ISD11)/NFS1 复合物结合，该复合物参与 Fe-S 簇生物发生。我们表明，与磷酸泛酰巯基乙胺辅酶结合的长酰基链的存在对于 ACPM 与蛋白复合物的对接很重要，并且我们提出 ACPM 和 LYRMs 的结合普遍基于新的蛋白-蛋白相互作用基序。
