topic 6-regulation of transport proteins Flashcards
(19 cards)
transport protein needs for regulation-NOT LEARNING
Responding to stimuli (external, internal)
Exert a cellular response
Preserve energy
Develop, evolve, adapt
ball and chain model
The ball-and-chain model explains how certain voltage-gated ion channels (like potassium channels) inactivate.
A “ball” region of the protein, connected by a flexible “chain,” swings into the channel pore after it opens and blocks ion flow.
This temporary inactivation prevents continuous ion passage. The ball binds through non-covalent interactions.
regulatory g-loop
The G-loop is a flexible loop in a protein (often part of an ion channel or GTPase), containing a glycine (G) residue, which is important for its function.
This loop plays a key role in regulating the protein’s activity, often by controlling conformational changes.
The G-loop is involved in switching the protein on and off. It often interacts with other regulatory molecules (like GTP or GDP) or phosphorylation events to modify the protein’s function.
Function:
In GTP-binding proteins (such as G-proteins), the G-loop interacts with the GTP/GDP to regulate the activation cycle.
In ion channels, the G-loop may be involved in regulating the opening and closing of the channel in response to signals.
The role of the NA+/k+ ATPase. b subunit in regulating transport proteins
The β subunit interacts with the α subunit’s transmembrane domain, modifying one or more intermediate conformational states (E1 and E2) during the pump cycle. This helps regulate the pump’s function and efficiency.
Regulation of ATP-synthase by inhibition by inhibitory factor 1 (IF1)
-associates with the f1 domain by insertion
- If1 disrupts the contact between B and Y subunits once disrupted ADP and ATP can still bind but It never get released
regulation by calmodulin
-calmodulin is general ca2+ dependent regulator of many channels and cellular processes
-very evolutionary conserved and has many different ways of working
-permiciousy in the molecules it can interact with. hence the many different ways
diffferent states of calmodulin
Calmodulin (CaM) exists in different forms based on how many Ca²⁺ ions are bound:
Apo state: no calcium bound
Partially loaded: some calcium bound
These calcium-bound states influence how CaM interacts with its target proteins.
CaM binds to short (~20 amino acid) helical motifs on target proteins. It has two lobes (N-terminal and C-terminal), each with calcium-binding sites. These lobes can function independently or cooperatively, depending on the target.
A central flexible helix connects the lobes, acting as a hinge. This structural plasticity allows CaM to adapt its shape to fit and regulate a wide range of proteins, such as ion channels and enzymes.
aquaporin channel regulated by calmodulin
Aquaporin 0 (AQP0) is a water channel in the eye. It’s controlled by a protein called calmodulin (CaM), which attaches to it when calcium levels are high. Two CaMs bind to one AQP0, and this binding makes the channel more likely to close. This helps the cell control how much water goes through, depending on conditions like calcium levels.
calmodulin regulation
Calmodulin (CaM) is a protein that senses calcium in the cell. When calcium binds to CaM, it changes shape and can then activate other proteins, like CaM-kinase (calmodulin-dependent kinase).
Chemical modification happens when CaM activates CaM-kinase, which then adds phosphate groups to target proteins (including sometimes CaM itself or associated proteins). This process is called phosphorylation, and it changes how those proteins behave—usually by turning them on or off.
In short:
Calcium binds to CaM → CaM activates CaM-kinase → CaM-kinase phosphorylates other proteins → cellular activity is regulated.
all the above are direct regulation
presence of small molecues in regulation
PIP₂ is a lipid found in the inner layer of the plasma membrane.
It binds directly to many ion channels and transporters, helping stabilize their open state.
When PIP₂ is broken down (e.g., by enzymes during signaling), the channels close or their activity changes.
Function: Acts like a “key” to keep channels open or responsive.
ATP (Adenosine Triphosphate):
ATP is energy currency, but it also acts as a regulator.
For ATP-dependent pumps (like the Na⁺/K⁺-ATPase), it directly powers the transport.
In some ion channels, ATP binds to regulatory sites to activate or inactivate them—even without being broken down.
what is cell trafficking
Translocation and Insertion
Proteins are made in the cytoplasm and moved (translocated) into the endoplasmic reticulum (ER).
They are then inserted into membranes (like the plasma membrane or organelles).
Removal by Endocytosis
Proteins can be removed from the membrane through endocytosis (a process that “swallows” parts of the membrane into the cell).
These proteins can then be recycled, reused, or broken down.
Gene Regulation
The amount of transporter or channel protein made is controlled at the gene level—so gene expression affects protein trafficking too.
Targeting and localisation signals
These are short amino acid sequences in a protein that tell the cell where the protein should go—for example, to the membrane, mitochondria, nucleus, etc.
Examples:
Na⁺/K⁺ ATPase (Sodium Pump)
Has specific targeting signals that direct it to the plasma membrane, where it functions to pump Na⁺ out and K⁺ in.
Proper localisation is essential—if it ends up in the wrong place, it can’t do its job.
Na⁺/Ca²⁺ Exchanger
Also has membrane-targeting sequences to ensure it goes to the right part of the membrane (e.g. heart muscle cells).
It helps remove Ca²⁺ from cells in exchange for Na⁺, so its location is critical for calcium regulation.
gene regulation
Subunit Variants
Some proteins are made of multiple subunits. Gene regulation allows the cell to use different variants of those subunits, leading to different functional forms of the protein.
Example: Hemoglobin has different subunits (like α and β), and their variants can be regulated to respond to different needs in the body.
Assembly
Gene regulation can influence how protein subunits assemble together to form a complete protein. This is essential for complex structures like enzymes or transporters.
Example: The Na⁺/K⁺ ATPase pump has multiple subunits that need to be assembled in the correct way for it to work.
Alternative Splicing
Alternative splicing is a process where one gene can produce multiple protein isoforms. This occurs when different exons (coding regions) of the gene are combined in various ways during RNA processing.
Example: Ion channels can have different spliced versions that function in various ways depending on the tissue type or cell condition.
Combinatorial Expression
This refers to the combination of different gene products or regulatory factors. Multiple genes may be expressed in different patterns to create complex systems.
Example: Different transcription factors may regulate multiple genes, leading to diverse outcomes in gene expression. This is especially important in processes like development or immune responses.
ATP-synthase and disease
-cause a mitrochondrial disease/disorder=
a disease caused by defects mitrochondrial functioning (often but not always) due to mutation in mitochondrial DNA
disease in transport protein
channelopathy: a disease caused by defects in (ion) channels
- can either have a gain in function or loss
-or things that arent transported etc..
disease in sodium-pump
e.g. digitoxigen = inhibits sodium-pump
-leads to an affcet in cardiac function. bradycardia etc..
long QT syndrome
-The cardiac action potential involves the combined effect of many ion transports (NA+, K+, CA2+). leads to a long QT interval
-can also be linked to genetics
