I. Review of proteins
A. Proteins are the most versatile molecules in your body, in fact the word “protein” is Greek for “of first importance”
B. Proteins are polymers of amino acids
-Primary structure– amino acids linked together by peptide bonds
-Secondary structure– coiled or folded shape held together by hydrogen bonds between the slightly negative C=O group of one peptide and the slightly positive N-H group of another one some distance away.
-Tertiary structure– more folding due to hydrophobic and hydrophilic regions interacting with surroundings
-Quaternary structure– Only some proteins (e.g. hemoglobin) have associations of polypeptide bonds by non-covalent forces with each other
-Many proteins can change conformation, especially tertiary structure triggered by voltage changes, hormone binding…
A. Molecules bind to transmembrane receptors and binding sites are the basis for many protein functions
B. Ligands are small molecules that bind to a protein receptor by van der Waal forces or electrical attraction.
1. L + R <–> L*R
2. Amount of L*R depends on concentrations of L and R and the affinity of L for R
3. Higher concentration of L increases the concentration of L*R; Lower concentration of L reduces the concentration of L*R
C. Receptor specificity
D. Receptor saturation
E. Receptor affinity
F. Receptor modulation
III. Mechanisms of cellular communication
A. Gap junctions– ring like protein, resembling segments of an orange, surrounding an aqueous pore in the lipid environments between 2 cells. Small molecules (ions, glucose, amino acids…) can pass directly from cytoplasm of one cell to the next through these pores.
1. Composed of interlocking cylindrical proteins called connexins, with each gap junction having one connexin from each cell coming together to form a hollow core
2. Excellent for flow of current (movement of ions between cells)
B. Chemical signals
1. Autocrine– chemical signal produced by a cell acts on the same cell
2. Paracrine– chemical signal produced by one cell affects a close neighbor
3. Endocrine– chemical signal produced by one cell travels in the bloodstream to another tissue leading to regulation of activities in distant tissues. Chemical signals are called hormones.
4. Receptors for chemical signals may be inside the cell or bound to membrane of target cell
a. Intracellular receptors –bind lipid soluble chemicals and the hormone-receptor complex causes the expression of target genes bringing about some response
b. Membrane receptors
–Lipid insoluble chemicals that cannot cross the membrane use these
-Ion channels are ligand-gated and are involved with signaling between electrically excitable cells
-G protein coupled receptors send signals to a G protein that initiates a second messenger pathway leading to a response in a target cell. Second messengers include cAMP, cGMP, inositol phospholipids and calcium
1) Membrane receptors coupled to G protein alpha, beta, gamma subunits
2) GDP is bound to alpha subunit without ligand present
3) With ligand binding, the alpha subunit releases GDP and attaches GTP and then separates from the rest of the G protein
4) This activated alpha subunit can bring about cellular responses such as activating adenylate cyclase to form cAMP from ATP. cAMP acts as second messenger to carry out cellular metabolic processes.
5) Activated alpha subunit removes a phosphate quickly from GTP as ligand is released thus returning G protein subunits to recombined resting state.
6) DAG (diacylglycerol) and IP3(inositol triphosphate) are other second messengers. Epinephrine activates G protein subunit which activates membrane enzyme, Phospholipase C. This enzyme then takes a constituent of cell membrane and coverts it to DAG and IP 3 which act as second messengers to cause a result such as smooth muscle contraction.
7) IP 3 can also cause Ca ++ release and Ca ++ can be a messenger initiating a variety of cell activities such as muscle contraction.
8) Receptors can directly activate intracellular mediators as well, as in cGMP acting as second messenger.
5. Summary of events initiated by hormones binding with membrane receptors involving second messengers
- Recognition of the signal by its receptor.
- Transduction (movement)of extracellular message into an intracellular (second) messenger.
- Transmission of the second messenger signal to the effector .
- Activation of protein kinases or phosphatases (kinases phosphorylate and phosphatases dephosphorylate).
- Response of the cell.
- Termination of the response.
C. Signals via receptor-enzymes Receptors can directly activate intracellular enzymes, as in example above with cGMP.
1. Extracellular ligand-binding domain
2. Transmembrane domain
3. Intracellular catalytic domain
4. Transmits a change of shape of receptor across the membrane thus activating the catalytic domain of the enzyme which leads to a cascade of phosphorylation of proteins causing a response in the target cell
D. Signal amplification –1 molecule of glucagon hormone may result in 1000 molecules of cAMP which activate protein kinases. Each protein kinase activates 1000 molecules of other enzymes and leads to the mobilization of 10,000 molecules of glucose! Thus a small stimulus leads to a huge effect.