As you read this text, the millions of cells that make up your body are working hard. In every cell there is active activity that keeps you alive, driven by machines made mostly of proteins. Some of these protein mechanisms are so important to living organisms that they have not changed over millions of years of evolution.
One of these ancient cellular machines is the membrane of the endoplasmic reticulum protein A complex (CEM) found in all eukaryotes, from fungi to insects, mice and humans. EMC, shaped like a bump-shaped tube, acts as a gateway between the interior of the cell and the outer membrane of the cell, and acts as a kind of boundary control through which only specific proteins can pass. EMC interacts with proteins involved in a variety of important processes, including the regulation of blood pressure and heart rate, and the levels of neurotransmitters such as serotonin and dopamine.
Now, in a new treatise published in the July issue of the journal Molecular cellThe researchers describe how cells assemble EMC from nine other perfectly combined small structures or protein subunits. The study was conducted in the laboratory of the California Institute of Technology of Rebecca Voorhees, assistant professor of biology. Biotechnology And researcher of the Institute of medical research of the inheritance.
The cell creates each of the nine EMC subunits individually. To form EMC, these distinct proteins must be in a relatively large area of the cell and come together. For example, imagine assembling an IKEA dresser from separate components (drawers (which also need to be assembled first), body, screws, knobs, etc.). Each part has an exact location throughout the structure. In a study published last year, Voorhees Labs created the first image of EMC with atomic-level detail, revealing a blueprint for its structure.
If the cell detects that the orphaned subunit is hanging for an extended period of time, the quality control process can destroy the subunit, much like throwing away the extra screws left by the IKEA assembly. CEM assembly must be done quickly.
“EMF is essential for all eukaryotes,” explains Voorhees. “If EMC is not assembled, the organism will not survive.”
To help them form the EMC together, each subunit has a specific location on its surface called a binding site, where it attaches to other specific subunit proteins. .. However, when it floats around a cell while waiting to bind to its counterpart, the subunit is vulnerable to accidental binding to other equally loose proteins in the cell. For example, imagine using a magnet to find a needle in a haystack. If there are other metal objects in the haystack that can stick to the magnet and cover its surface, preventing it from bonding to the needle you are looking for, you may not be able to find it . Therefore, EMC subunits (and other proteins) need a way to protect the binding site until they are ready to bind to the right partner.
This is where proteins called assembly factors come in. Assembly factor proteins physically cover and protect sensitive binding sites, but they do not stay there forever. When the subunit finds the right protein to bind to, it peels off like a ribbon and the two proteins become an “instant adhesive” at the binding site.
This multi-step assembly process is the main research topic of the Voorhees Institute. In the new study, the team set out to find out how EMC was assembled correctly. This group specifically focused on one subunit, EMC2. It binds to 6 of the other 8 EMC subunits and therefore serves as the backbone of the EMC composite architecture.
In this study, the team found that another protein, called WNK1, acts as an assembly factor for EMC2 and temporarily protects its sensitive binding site until it can encounter other subunits. EMC. .. It was amazing. Although WNK1 is known to play several important roles in the cell (eg, mutations in WNK1 lead to congenital hypertension), there was no evidence of protection of the EMC2 binding site.
WNK1 is a relatively large protein, and most researchers focus on studying a small area of the protein called the kinase that catalyzes the reaction. However, WNK1 also had a long “tail” and its purpose was not understood. This new study shows that part of the tail is responsible for covering the EMC2 binding site.
“People have been studying kinase domains for years, but no one really knew what the WNK1 tail was doing,” says Voorhees. “The tail is about 10 times heavier than the kinase region, so it’s huge compared to what we understand. Surprisingly, part of the tail binds EMC2. It was an unprecedented game. It was previously thought to have some function, but it is found in all higher eukaryotes. In future research, WNK1 is therefore involved in EMC. I am very interested in understanding why I am. “
The title of this article is “WNK1 is an Aggregated Factor in the Human ER Membrane Protein Complex”.
Tino Pleiner et al, WNK1, is an aggregate factor of the human ER membrane protein complex. Molecular cell (2021). DOI: 10.1016 / j.molcel.2021.04.013
California Institute of Technology
Quote: Some Assembly Required: How a Cellular Machine Is Built (July 9, 2021) from https://phys.org/news/2021-07-required-cellular-machine.html Obtained July 9, 2021
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