Gabs Protein Structure and Function Pt 2 Lecture 9 Covalent modi cations to proteins phosphorylation addition of phosphate phosphate is negatively charged and is added to hydroxyl group addition of a negatively charged phosphate group to the R group of serine threonine tyrosine bacterial cells can phosphorylate histidine residues serine R CH2 OH phosphoreserine R CH2 O PO3 2 phosphate usually comes from ATP forms the phosphorylated amino acid residue and ADP reaction is catalyzed by a class of protein enzymes known as kinases kinase subfamilies tyrosine kinase MAP kinase cyclin dependent kinase receptor serine kinase phosphorylation is reversible phosphatases catalyzed the removal of a phosphate phosphorylation drives many changes in protein structure and activity the addition of each phosphate group adds 2 negative charges subsequently ionic bonds can be formed with neighboring positively charged amino acid R groups or with ions in solution this can cause major structural changes changes in activity or changes in protein solubility the phosphate group may create a new recognition site allowing other proteins to bind to the phosphorylated protein glycosylation addition of sugar carbohydrate chains of 2 60 sugar monomers can be added to the OH group of serine O linked or the NH2 group of asparagine N linked glycoprotein formed by the addition of carbohydrate to a protein common process on extracellular portion of transmembrane proteins addition of lipids or glycolipids 1 Gabs lipoprotein formed by the addition of fatty acids or phospholipids to N terminal glycine residue or cysteine the fatty acid chain can anchor a protein to a membrane by inserting itself into the hydrophobic core of a biological membrane ubiquitylation addition of ubiquitin ubiquitin is a small cyctosolic protein made of 76 amino acids attaches covalently to proteins reversible can un attach serves as a tag that can mark protein for degradation polyubiquitylation or direct protein to a speci c location in the cell monoubiquitylation occurs at lysine amino acids catalyzed by ubiquitin ligases a class of enzymes works by forming a multi subunit protein complex with other proteins that enable them to bind the target and the ubiquitin together this covalent modi cation is an actual protein A protein modi cation can promote or inhibit the addition of another modi cation the addition and removal of modi cation groups changes the behavior or stability of a protein Proteins interact with other molecules ligands molecules ions small organic molecules and other proteins which bind to the protein in question as ligand bonding is generally done with non covalent bonds it is reversible the strength of ligand binding molecules are always in motion and bumping into each other so the bond must be strong enough to withstand the jolting of molecular motions strength is achieved by the formation of several non covalent bonds and 3D complementarity of binding K the strength of binding K association K disassociation smaller K disassociation means a larger binding strength 2 Gabs 3D binding a reason why correct protein folding is important for function the ligand binding sites are often far apart on a protein s primary binding sequence so proper folding brings the sites close together physical interaction with other molecules determines a proteins biological properties the interaction between a protein and its ligand can be weak and short lived or tight and stable and is always speci c any given protein can only interact with a few different molecules out of the thousands in its environment What do proteins do once their bound to a ligand regulation by binding to phosphorylated dephosphorylated forms of another nucleotide such as guanosine triphosphate an activated energy carrier which can bind to proteins to regulate their activity the protein can avoid using ATP GTPases or G proteins bind to GTP to become activated then they hydrolyze GTP into GDP making the protein inactive Ras family of GTPases involved in cell signaling can receive signals activate other proteins in response to the signals received and cause cancer when overative many larger proteins have Ras like GTPase domains as part of 3D structure Ef Tu elongation factor in protein synthesis Proteins can act as molecular integrators by having multiple modi cation interaction sites a modi cation or interaction generally results from activity of a speci c external signaling pathway or intracellular state from a modi cation interaction protein function can in uenced positively or negatively by itself or in concert with others converging signals from various modi cations interactions are integrated in the nal state of protein activity Proteins often function as supramacromolecular assemblies examples of this are microtubules and nuclear pores 3 Identical proteins binding together can form laments The proteins involved have complementary binding sites From there the protein subunits can form hexagonal sheets or helical tubes Gabs 4
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