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Press the pause button: a glimpse of the moment when the membrane protein complex is assembled

 Last Update: 2021-09-10
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Schematic diagram of the assembly of the mitochondrial outer membrane translocase complex

For many years, scientists have been trying to "see" the mystery of this high-precision assembly line

On August 27, "Science" published online the latest results of Professor Yin Ping's research group from the Hubei Hongshan Laboratory, the State Key Laboratory of Crop Genetic Improvement of Huazhong Agricultural University, and the Protein Science Research Team of the School of Life Science and Technology

Highly dynamic assembly process

The mitochondria is a double-membrane organelle in the cytoplasm

"The mitochondrial outer membrane translocase complex is like a transport vehicle

Qiu Jian, a professor at Xiangya Hospital of Central South University, told the Chinese Journal of Science that many scientists have tried to use biochemical methods to analyze the composition and assembly of the mitochondrial outer membrane translocase complex, but the assembly of the mitochondrial outer membrane translocase complex It is a transient, multi-step and highly dynamic process, and it is difficult to capture the transient structure of its assembly

Moreover, the mitochondrial outer membrane translocase complex is the gateway for protein precursors to enter the mitochondria.

Studies have shown that the assembly of the mitochondrial outer membrane translocase complex requires the assistance of the mitochondrial sorting and assembly machinery (SAM)

However, "the molecular mechanism of how the mitochondrial sorting assembly machine assists the assembly of the mitochondrial outer membrane translocase complex is still unclear

"Press the pause button"

"Our method is to press the pause button for the assembly process

Since 2019, Yin Ping's research group has begun to pay attention to the research of related issues

"Interestingly, we failed to obtain the core of the translocase complex of the outer mitochondrial membrane

Wang Qiang, the co-first author of the paper and a PhD from the School of Life Sciences of Huazhong Agricultural University, said that they took a different approach and reconstructed the assembly process using a mammalian cell recombination expression system and achieved precise control.

Multiple intermediate states of the complex assembly process and obtain its protein samples

Yin Ping explained that the mitochondrial outer membrane translocase complex (TOM) is imagined as a transport vehicle.
The mitochondrial sorting and assembly machine is like a "manipulator" on the assembly line.
The vehicle "shell" Tom40 is first installed, and then two Two "wheels" Tom5 and Tom6; then use the "wrench" Tom7 to remove the assembled "housing" and "wheels" from the "manipulator"
.
They will then proceed to the next assembly step
.

"We have now figured out how the mitochondrial outer membrane translocase complex is assembled and released on the'pipeline'
.
" Yin Ping said
.

The assembly of the mitochondrial outer membrane translocator complex
.
Photo courtesy of the interviewee

Ingenious ideas are worth learning

"This is a very cleverly designed experiment.
It put a set of yeast protein folding machines into human mitochondria, and found things that others could not catch, filling the gap in this field
.
" Qiu Jian said
.

Yin Ping believes that the mitochondrial outer membrane translocase complex is responsible for the important work of transporting foreign protein precursors to the inside of the mitochondria, and figuring out its assembly process can help scientists better explore the biogenesis of mitochondrial proteins, and provide treatment and treatment for mitochondrial diseases.
Crop genetic improvement provides a theoretical basis
.
"The methods and results of this research will help provide a new perspective for the study of the mechanism of chloroplast protein biogenesis
.
"

The mitochondrial outer membrane translocase complex assembles an intermediate three-dimensional structure
.
Photo courtesy of the interviewee

In addition, Yin Ping said that the method of putting the components of the yeast mitochondrial outer membrane translocase complex into mammalian mitochondria for assembly has solved the problem that traditional methods cannot capture transients
.

Qiu Jian told China Science Daily that many processes in life activities are highly dynamic, and it is difficult for traditional biochemical methods to capture a certain transient
.

"This is a good inspiration.
Similar problems in other systems, involving transient processes, may be able to find answers through similar ideas
.
" Qiu Jian said
.

Yin Ping said that in the next step they will perfect the whole process of assembly of the mitochondrial outer membrane translocase complex
.
He hopes that the assembly process of the mitochondrial outer membrane translocase complex can provide a useful understanding for the design of membrane proteins and the creation of new drugs
.
(Source: China Science News Li Chen)

Related paper information: https://doi.
org/10.
1126/science.
abh0704

https://doi.
org/10.
1126/science.
abh0704

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