CryoEM reveals oligomeric isomers of a multienzyme complex and assembly mechanics

被引：4
作者：
Lee, Jane K. J. [1 ,2 ,3 ]
Liu, Yun-Tao [1 ,2 ]
Hu, Jason J. [1 ,2 ,4 ]
Aphasizheva, Inna [5 ]
Aphasizhev, Ruslan [5 ,6 ]
Zhou, Z. Hong [1 ,2 ]
机构：
[1] Univ Calif Los Angeles UCLA, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA
[2] UCLA, Calif Nanosyst Inst, Los Angeles, CA 90095 USA
[3] UCLA, Dept Psychol, Los Angeles, CA 90095 USA
[4] UCLA, Dept Math, Los Angeles, CA 90095 USA
[5] Boston Univ Med Campus BUMC, Dept Mol & Cell Biol, Boston, MA 02118 USA
[6] BUMC, Dept Biochem, Boston, MA 02118 USA
来源：
JOURNAL OF STRUCTURAL BIOLOGY-X | 2023年 / 7卷
基金：
美国国家卫生研究院;
关键词：
Propionyl-CoA; Statistical mechanics; Thermodynamics; Rate constant; Conformation; PROPIONYL-COA CARBOXYLASE; 3-METHYLCROTONYL-COA CARBOXYLASE; ALPHA(6)BETA(6) HOLOENZYME; CRYSTAL-STRUCTURE; COENZYME; SPLICEOSOME; FEATURES; ENZYMES; FORMS;
D O I：
10.1016/j.yjsbx.2023.100088
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Propionyl-CoA carboxylase (PCC) is a multienzyme complex consisting of up to six alpha-subunits and six beta-subunits. Belonging to a metabolic pathway converging on the citric acid cycle, it is present in most forms of life and irregularities in its assembly lead to serious illness in humans, known as propionic acidemia. Here, we report the cryogenic electron microscopy (cryoEM) structures and assembly of different oligomeric isomers of endogenous PCC from the parasitic protozoan Leishmania tarentolae (LtPCC). These structures and their statistical distribution reveal the mechanics of PCC assembly and disassembly at equilibrium. We show that, in solution, endogenous LtPCC beta-subunits form stable homohexamers, to which different numbers of alpha-subunits attach. Sorting LtPCC particles into seven classes (i.e., oligomeric formulae alpha 0 beta 6, alpha 1 beta 6, alpha 2 beta 6, alpha 3 beta 6, alpha 4 beta 6, alpha 5 beta 6, alpha 6 beta 6) enables formulation of a model for PCC assembly. Our results suggest how multimerization regulates PCC enzymatic activity and showcase the utility of cryoEM in revealing the statistical mechanics of reaction pathways.
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页数：9
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