Proteins: What are proteins and what do they do?
They're heteropolymers of amino acids that play a crucial role in nearly every biological process. I consider them to be molecular robots. They function in a myriad of ways which can be generally categorized as follows:
1. Enzyme catalysis. Most chemical reactions in biological systems are carried out by proteins (or more specifically--enzymes). Some enzymes perform simple processes such as isomerization of hydroxyl groups, hydration of CO2, and phosphorylation reactions. Others accomplish more difficult tasks, such as replicating an entire chromosome of billions of DNA bases with incredible fidelity. Importantly, in the absence of enzymes many biological processes would not occur. Enzymes catalyze reaction rates by at least 1 million-fold.
2. Transport and storage. Many small molecules and ions are transported by specific proteins. Hemoglobin transports oxygen throughout the body from within red blood cells. Myoglobin "steals" it away from hemoglobin and delivers it to muscle tissue; Iron is stored in the liver complexed to a protein called ferritin which is released on demand as tissues are being constructed or reconstructed; Calcium is captured by calcitonin and deposited to form bones.
3. Coordinated motion. Proteins known as flagella propel bacteria to facilitate nutrient assimilation, protein muscle fibers contract to accomplish work, while other proteins move and separate chromosomal DNA fibers just prior to cell division.
4. Mechanical support. The high tensile strength of skin and bone is due to the presence of collagen, a fibrous protein (osteogenesis imperfectii). Spectrin is a matrix protein in cells which gives a rigid shape to membrane structure. Hair is composed of keratin, another rigid protein.
5. Immune protection. Antibodies are produced by blood cells and these proteins react with foreign substances to mark them for removal from the body. Other proteins are expressed on cell surfaces which distinguish you and me--self and non-self.
6. Generation and transmission of nerve impulses. Rhodopsin in the eye is our "Photoreceptor". Receptors on nerve cells bind acetylcholine and transmit nerve impulses.
Why is it important to know a protein's amino acid sequence?
1) Often sequence information provides clues to protein function, catalytic properties and mechanism.
2) Proteins with novel properties can be produced with slight modifications to the sequence -- so-called "Protein Engineering" (i.e., Spray and Wash).
3) Sequence determination is key to molecular pathology and molecular medicine.
Alterations in the amino acid sequence can produce abnormal protein function and disease. Examples include sickle cell anemia and cystic fibrosis, both are brought about by changes in a single amino acid residue.
4) Molecular evolution. Conservation of protein sequence between species can only have occured through co-evolution-a new and fluorishing field-molecular palentology.
Protein modification and cleavage -- Post-translational modifications.
1). acetylation - In eucaryotic cells, many proteins are acetylated at the amino-terminus which is believed to confer resistance to proteases.
2). hydroxylation - In newly synthesized collagen, many of the proline residues are hydroxylated to form hydroxyproline. In complete maturation of collagen fibers, hydroxyproline residues form interstrand hydrogen bonds which lend added stability. Vitamin C is critical for this hydroxylation and absence of it from the diet causes scruvy.
3). carboxylation - Carboxylation of glutamate residue in prothrombin is essential for producing a fully functional protein. Absence thereof can cause hemorrhage or hemophilia.
4). Addition of carbohydrate units or fatty acid units - Such modifications greatly affect the hydrophobic/hydrophilic nature of a protein. Certain carbohydrate modifications mark a protein for secretion, i.e., antibodies.
5). Phosphorylation - Many growth factors and hormones cause the phosphorylation of specific serine or tyrosine residues of enzymes and trigger or greatly alter enzyme activity or function. Most recently, it has become clear that some cancer causing genes (oncogenes) act by stimulating excessive phosphorylation of tyrosine residues. 6). Cleavage of the peptide bond - Many proteins are synthesized as inactive precursors and activated on cleavage at a specific internal peptide bond. Most exemplary are the proteases which are produced and stored in the pancreas. They are only activated after they're dumped into the intestines where they are activated by peptide bond cleavage. In HIV, several viral proteins are produced as a single unit which requires selective cleavage to reproduce the virus.