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Proteins can be big or small, mostly hydrophilic or mostly hydrophobic, exist alone or as part of a multi-unit structure, and change shape frequently or remain virtually immobile. All of these differences arise from the unique amino acid sequences that make up proteins. Fully folded proteins also have distinct surface characteristics that determine which other molecules they interact with. When proteins bind with other molecules, their conformation can change in subtle or dramatic ways.

Not surprisingly, protein functions are as diverse as protein structures. For example, structural proteins maintain cell shape, akin to a skeleton, and they compose structural elements in connective tissues like cartilage and bone in vertebrates. Enzymes are another type of protein, and these molecules catalyze the biochemical reactions that occur in cells. Yet other proteins work as monitors, changing their shape and activity in response to metabolic signals or messages from outside the cell. Cells also secrete various proteins that become part of the extracellular matrix or are involved in intercellular communication.

Proteins are sometimes altered after translation and folding are complete. In such cases, so-called transferase enzymes add small modifier groups, such as phosphates or carboxyl groups, to the protein. These modifications often shift protein conformation and act as molecular switches that turn the activity of a protein on or off. Many post-translational modifications are reversible, although different enzymes catalyze the reverse reactions. For example, enzymes called kinases add phosphate groups to proteins, but enzymes called phosphatases are required to remove these phosphate groups (Figure 1).

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Proteins can be big or small, mostly hydrophilic or mostly hydrophobic, exist alone or as part of a multi-unit structure, and change shape frequently or remain virtually immobile. All of these differences arise from the unique amino acid sequences that make up proteins.

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"We believe this study gives us a better understanding of the effects of GBA1 mutation and its role in the development and progress of Parkinson's disease," says Han Seok Ko, Ph.D., associate professor of neurology at the Johns Hopkins University School of Medicine Institute for Cell Engineering.

According to Ko, Lewy bodies are made of clumps of proteins known as alpha-synucleins. In healthy cells, single alpha-synuclein proteins tether together in groups of four, called tetramers, which are more resistant to aggregating in the brain. However, in Parkinson's disease, single alpha-synucleins stick together in the cell membranes, making it impossible for neurons to properly communicate with one another.

The cellular membrane is like a mosaic where fatty molecules act as the cement that holds proteins in an intricate design. In healthy cells, GBA1 ensures that the "cement" is mixed properly to hold the mosaic together. Ko says he and his team theorized that when GBA1 is mutated, this process goes awry and the cell membrane's composition is changed-determining whether the alpha-synuclein tetramers can stay in place.

To test this theory, Ko and his team studied the effects of removing GBA1 in lab-grown human neuron cells using CRISPR-Cas9, a gene editing technology. They treated half of the "edited" cells with miglustat, a drug primarily used to block the production of fatty molecules, and observed the protein levels in the cell.

The researchers found that deleting GBA1 increased levels of a particular fatty molecule called glucosylceramide. When glucosylceramide levels rose, they reported, the number of stable alpha-synuclein tetramers fell. The levels returned to nearly normal with miglustat treatment.

Ko and his team believe that increased levels of glucosylceramide destabilized the cellular membrane mix and caused alpha-synuclein tetramers to fall out of the mosaic and break into single alpha-synucleins.

"This is interesting because past studies focused on how GBA1 mutations caused single alpha-synuclein aggregation, but not its effects on the stable tetramers," says Ko.

The researchers then tested their idea in human neurons collected from patients with GBA1-associated Parkinson's disease and found that-like the lab-grown cells-the human Parkinson's disease cells had about two times more glucosylceramide in their membranes than cells without the Parkinson's mutation. Similarly, the number of single alpha-synucleins also increased in these cells, and treatment with miglustat effectively restored alpha-synuclein tetramers to near-normal levels.

In a final test, the researchers wanted to investigate whether replacing GBA1 could restore the function of the membrane mix. After using a virus engineered to add a functional copy of the GBA1 gene into cells, Ko found that alpha-synuclein tetramers returned to near-normal levels and the amount of alpha-synuclein aggregates was reduced.

In the future, the researchers intend to further investigate the impact the GBA1 protein has on the formation of alpha-synuclein tetramers and overall neuronal health.

First observed in 2004, GBA1-associated Parkinson's disease is the most common of the currently known Parkinson's disease mutations. According to the researchers, 5 to 10 percent of Parkinson's disease patients carry a GBA1 mutation.

Other researchers involved in this study include Sangjune Kim, Seung Pil Yun, Saebom Lee, George Essien Umanah, Veera Venkata Ratnam Bandaru, Xiling Yin, Peter Rhee, Senthilkumar S. Karuppagounder, Seung-Hwan Kwon, Hojae Lee, Xiaobo Mao, Donghoon Kim, Akhilesh Pandey, Gabsang Lee, Valina L. Dawson and Ted M. Dawson of the Johns Hopkins University School of Medicine.

This work was supported by The Maryland Stem Cell Research Foundation (2012-MSCRFE-0059 & 2007-MSCRFI-0420-00), the National Institute on Neurological Disorders and Stroke (1RC2NS07027, 1U24NS078338, NS082205, NS098006, NS093213, NS38377), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR070751), the National Institutes on Aging (AG005146), the Morris K. Udall Parkinson's Disease Research Center and the JPB Foundation.

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Faulty Cellular Membrane "Mix" Linked To Parkinson's Disease

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"We believe this study gives us a better understanding of the effects of GBA1 mutation and its role in the development and progress of Parkinson's disease," says Han Seok Ko, Ph.D., associate professor of neurology at the Johns Hopkins University School of Medicine Institute for Cell Engineering.

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The plasma membrane is made up of a phospholipid bilayer. These have 2 parts, a hydrophobic (water-hating) part, and a hydrophilic (water-loving) part.

The hydrophilic heads, comprised of a phosphate group, face the outside and inside of the cell, where water is present. The hydrophobic tails, comprised of fatty acids, face inward and do not interact with water.

Image courtesy of Wikimedia Commons

As seen below, there are proteins embedded into the plasma membrane. These proteins can be hydrophobic, hydrophilic, charged, uncharged, polar, or non-polar depending on the configuration of the amino acids in the protein.

Image courtesy of Wikimedia Commons

The cell membrane also has glycoproteins and glycolipids attached to it along with steroids. These groups help with cell signaling and the attachment of the cell to other structures.

Models of the plasma membrane are given the name: fluid mosaic model. This represents the fact that the membrane is fluid and somewhat moveable. The proteins embedded in the membrane, which serve a variety of functions, create the mosaic portion of the name.
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Membrane Permeability

Thanks to the structure of the membrane, with the hydrophobic tails and hydrophilic heads, the cellular membrane has selective permeability. This allows some substances to cross easily, while others may not be able to cross or may require a special transport protein to do so.

The membrane acts like a barrier separating the inside of the cell from the external environment of the cell.

Small, non-polar molecules are able to freely cross the cell membrane, while polar or charged molecules require transport proteins to cross. If a molecule is small, polar, and uncharged (like water!) it may be able to pass through the membrane in small quantities but requires a transport protein to move across in any larger quantities.

The hydrophobic fatty acid tails are what controls the movement of substances described above. They repel charged and polar molecules and make it very challenging for them to come across.

Image courtesy of Wikimedia Commons

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The plasma membrane is made up of a phospholipid bilayer. These have 2 parts, a hydrophobic (water-hating) part, and a hydrophilic (water-loving) part. The hydrophilic heads, comprised of a phosphate group, face the outside and inside of the cell, where water is present.

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cell membrane, thin membrane that surrounds every living cell, delimiting the cell from the environment around it. Enclosed by this cell membrane (also known as the plasma membrane) are the cell's constituents, often large, water-soluble, highly charged molecules such as proteins, nucleic acids, carbohydrates, and substances involved in cellular metabolism. Outside the cell, in the surrounding water-based environment, are ions, acids, and alkalis that are toxic to the cell, as well as nutrients that the cell must absorb in order to live and grow. The cell membrane, therefore, has two functions: first, to be a barrier keeping the constituents of the cell in and unwanted substances out and, second, to be a gate allowing transport into the cell of essential nutrients and movement from the cell of waste products.

Cell membranes are composed primarily of fatty-acid-based lipids and proteins. Membrane lipids are principally of two types, phospholipids and sterols (generally cholesterol). Both types share the defining characteristic of lipids-they dissolve readily in organic solvents-but in addition they both have a region that is attracted to and soluble in water. This "amphiphilic" property (having a dual attraction; i.e., containing both a lipid-soluble and a water-soluble region) is basic to the role of lipids as building blocks of cellular membranes. Membrane proteins are also of two general types. One type, called the extrinsic proteins, is loosely attached by ionic bonds or calcium bridges to the electrically charged phosphoryl surface of the bilayer. They can also attach to the second type of protein, called the intrinsic proteins. The intrinsic proteins, as their name implies, are firmly embedded within the phospholipid bilayer. In general, membranes actively involved in metabolism contain a higher proportion of protein.

The chemical structure of the cell membrane makes it remarkably flexible, the ideal boundary for rapidly growing and dividing cells. Yet the membrane is also a formidable barrier, allowing some dissolved substances, or solutes, to pass while blocking others. Lipid-soluble molecules and some small molecules can permeate the membrane, but the lipid bilayer effectively repels the many large, water-soluble molecules and electrically charged ions that the cell must import or export in order to live. Transport of these vital substances is carried out by certain classes of intrinsic proteins that form a variety of transport systems: some are open channels, which allow ions to diffuse directly into the cell; others are "facilitators," which help solutes diffuse past the lipid screen; yet others are "pumps," which force solutes through the membrane when they are not concentrated enough to diffuse spontaneously. Particles too large to be diffused or pumped are often swallowed or disgorged whole by an opening and closing of the membrane.

In bringing about transmembrane movements of large molecules, the cell membrane itself undergoes concerted movements during which part of the fluid medium outside of the cell is internalized ( endocytosis) or part of the cell's internal medium is externalized ( exocytosis). These movements involve a fusion between membrane surfaces, followed by the re-formation of intact membranes.

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Cell membrane | Definition, Function, & Structure

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Cell membrane, thin membrane that surrounds every living cell. The cell membrane functions as a barrier, keeping cell constituents in and unwanted substances out, and as a gate, allowing transport into the cell of essential nutrients and movement from the cell of waste products.

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“Cell Membrane.” Encyclopaedia Britannica. Encyclopaedia Britannica, inc. Accessed October 6, 2021. https://www.britannica.com/science/cell-membrane.

“Plasma Membranes.” Fiveable. Accessed October 6, 2021. https://fiveable.me/ap-bio/unit-2/plasma-membranes/study-guide/1aW0ZDGzS56ism3BJwTi.

“Faulty Cellular Membrane ‘Mix’ Linked to Parkinson's Disease.” Johns Hopkins Medicine Newsroom, March 15, 2018. https://www.hopkinsmedicine.org/news/newsroom/news-releases/faulty-cellular-membrane-mix-linked-to-parkinsons-disease.

“Protein Function.” Nature news. Nature Publishing Group. Accessed October 6, 2021. https://www.nature.com/scitable/topicpage/protein-function-14123348/.

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Diseases occur when the cell membrane malfunctions

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Diseases occur when the cell membrane malfunctions

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For example, Parkinson can occur when the gene GBA1 mutates. This causes a cell membranes composition to change and does not allow for alpha-synucleins to form tetramers on the cell membrane and makes it harder for neurons to communicate.

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If a cell was a club, the membrane would be the bouncer. It chooses who can come into the cell and prevents things that could harm the cell from entering. Without the cell membrane the cell's organelles would not have their resources and would be exposed to viruses and harmful materials.

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All cells that have ever existed have had cell membranes, they are necessary for life to exist in the first place

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Other organelles depend on the function of the membrane.

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Other organelles depend on the function of the membrane.

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If the cell membrane did not exist, organelles would have nothing providing them with their nutrients and expelling their waste, organelles would not be in a cell in the first place because nothing would be holding them together and protecting them.

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The cell membrane is the best organelle!

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The cell membrane is the best organelle!

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Your cell membrane will come with many phospholipids, (they'll form a bilayer just give them time), proteins and cholesterol (the good kind).

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There are two types of Membrane Proteins:

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There are two types of Membrane Proteins:

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Extrinsic proteins are loosely attached by ionic bonds or calcium bridges to the electrically charged phosphoric surface of the bilayer, inside or out. They can also attach to Intrinsic proteins.

Intrinsic proteins are embedded within the bilayer and are usually exposed on both sides.

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Intracellular proteins hold cells together.

Enzymatic Proteins build things or break them down.

Transport Proteins allow for things to get through the membrane

Cell-Cell Recognition Proteins allows other cells to identify the cells.

Anchorage/Attachment proteins serve as the foundation to build things like cytoskeletons and proteins

Signal Transduction Proteins allows signals to be transmitted acting as a middleman for communication.

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Proteins let the good things in and preforms specific functions

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Proteins let the good things in and preforms specific functions

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Proteins are responsible for very specific functions and some, specifically transport proteins, are what allows for specific materials to enter or exit the cell. Things like O2 and nutrients are let through the cell and waste is removed because of these proteins. Proteins do have other functions, like forming structure and creating, relaying, and receiving information.

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The majority of a cell membrane is a bilayer made up of two layers of phospholipids called a "bilayer."

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The majority of a cell membrane is a bilayer made up of two layers of phospholipids called a "bilayer."

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The phospholipid bilayer keeps bad things out.

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The phospholipid bilayer keeps bad things out.

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Phospholipids are amphipathic, meaning they have polar and non-polar parts. The non-polar tails would not let anything polar through, and non-polar molecules usually can not fit through the gaps in the phosphate heads, however non-polar gases can.

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Cellular Membranes are flexible and strong, it separates the cell from the its environment.

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Cellular Membranes are flexible and strong, it separates the cell from the its environment.

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Attractions keep the phospholipids that make up the bilayer together, they are not anchored together so it is very fluid and flexible. This allows the cells to move and replicate.