L3 proteins and amino acids (PF1)

• Proteins are the main functional components of the cell and provide shape and structure.
• Proteins are the most abundant macromolecule in the cell and have many diverse structures, meaning they have multiple functions.
• Proteins undertake most functions of the cell including enzymes that catalyze cell chemical reactions, membrane proteins that form communication channels to communicate with the environment, and other proteins that transport cargo and mechanical forces.
• Proteins acquire function by folding into a 3D conformation because folding provides physical stability and the sequence of amino acids of a protein determines its structure, function and localization.
• Proteins are polymers made of 20 different amino acids.
• The general formula of an amino acid is: amino group, a carboxyl group (acidic), a hydrogen, alpha carbon and a side chain group.
• At pH 7, the amino and carboxyl groups of an amino acid are ionized, meaning that the total charge of the amino acid at pH 7 depends on the side chain.
• The characteristics of amino acid side chains are whether they are hydrophobic, polar, or charged; small or large; covalently linked into polypeptides.
• Four groups of amino acids are polar amino acids: asparagine, glutamine, serine, threonine, tyrosine.
• These amino acids form hydrogen bonds.
• Asparagine and glutamine have amide chains.
• Serine, threonine and tyrosine have hydroxyl groups.
• Homology (sequence similarity) indicates evolutionary conservation suggesting a common structure or function.
• Some domains are combined and conserved together and are found in many different proteins.
• A protein family is a set of proteins or domains which have homologous sequences and structures; they often have related functions; an organism can have several proteins from the same family and proteins from the same family can be found in different organisms.
• If polypeptides have no sequence similarity, they are considered to be divergent.
• A domain is an independently folded unit within a protein; proteins can have one or multiple domains; different domains in a protein often have different functions.
• Many biological functions require non-covalent protein interactions; sometimes protein interactions are specific, meaning only certain molecular surfaces are bound, sometimes protein interactions are transient, meaning the interactions form and break apart quickly; thermal motion means all molecules are constantly moving, tumbling and colliding.
• “Modular” domains often form reversible, specific, non-covalent contacts with other molecules (including other proteins, lipids, carbs, RNA, DNA and other cofactors).
• There are four main ways to visualize proteins in different types of diagrams: the polypeptide backbone can be the only thing represented in a ribbon diagram, the polypeptide backbone and the secondary structure are shown in a stick diagram, the amino acid side chains are included in a stick diagram, and the space filling model shows the mass of atoms to create the protein.
• Examples of some domains include the transcription activation domain and DNA binding domain in transcription factors.
• The sequences of different polypeptides can be compared to align identical (same amino acids) or similar amino acids (same properties).
• Charged amino acids are basic and acidic amino acids and can be engaged in ionic or electrostatic interactions.
• Basic amino acids include lysine, arginine and histidine.
• Acidic amino acids include aspartate and glutamate.
• Hydrophobic non-polar amino acids include alanine, valine, proline, phenylalanine, glycine, cysteine, leucine, isoleucine, methionine, tryptophan.
• Glycine will be found everywhere, not only in the inside of the protein.
• Protein folding occurs in the ER lumen or exterior of the cell, not in the cytosol.
• Beta sheets are neighboring segments of the polypeptide backbone.
• Beta sheets have hydrogen bonds between the backbone strands and have side chains on alternate sides, making it a very rigid structure.
• All amino acids can engage in secondary structures, which results from hydrogen bonding between N-H and C=O groups in the polypeptide backbone.
• Side chains of the alpha-helix point outwards.
• Tertiary structure is the complete three-dimensional arrangement of the polypeptide, with secondary structure elements packed against each other to form the tertiary structure.
• A dimer is two polypeptide subunits, a trimer is three polypeptide subunits, a tetramer is four, 5-mer, 6-mer, etc.
• Loops are amino acids that are not part of the secondary structure and can be flexible, also called intrinsically disordered region.
• Long-range contacts between residues that are far apart in the primary sequence form the tertiary structure.
• Hydrophobic contacts between secondary elements form the tertiary structure.
• The backbone of the alpha-helix is coiled in an alpha helix, with hydrogen bonds between carbonyl oxygen and amine hydrogen formed every 4 peptide bonds in each turn of the helix.
• The backbone of the beta sheet is extended almost straight, with several strands packing sideways into a beta sheet.
• The alpha-helix is a single polypeptide chain that twists around on itself.