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STRUKTUR DAN FUNGSI PROTEIN Joko Marwoto

To a large extent cells are made of proteins.

Protein determine the shape and structure of the cell and also serve as instruments of molecular recognition and catalysis.

In computer terminology, the nucleic acids represent the “software” – instructions that a cell receives from its parent. Proteins make up the “hardware”- the physical apparatus that executes the program stored in the memory.

DNA and RNA consist of a series of nucleotides, all being chemically very similar to one another, assembled into giant molecules having much the same chemistry whatever their sequence.

PROTEIN are made from an assortment of 20 very different amino acids, each with a distinct chemical personality. This variety allows for enormous versatility in the chemical properties of different proteins.

The shape of a Protein Molecule Is Determined by Its Amino Acid Sequence

Many of the bonds in a long polypeptide chain allow free rotation of the atoms they , giving the protein backbone great flexibility.

In principle then, any protein molecule can adopt an enormous number different shapes, or conformation of a protein unusual stability.

The folding of protein into a globular conformation

The polar amino acid side chains tend to be exposed on the outside of the protein; the nonpolar amino acid side chains are buried on the inside to form a hydrophocic core “ hidden” from the water.

Common Folding Patterns Recur in Different Protein Chains More than 200 proteins have been completely analyzed by x-ray diffraction analysis. Each of these proteins has a specific conformation.

The structure of the beta-sheet makes up extensive regions of the core of most (though not all) globular proteins. The three dimensional conformation of the protein egg-white lysozyme as seen in four commonly used representations.

An alfa-helix is generated when a single polypeptide chain turns regularly about itself to make a rigid cylinder in which each peptide bond is regularly hydrogenbounded to other peptide bonds elsewhere in the chain.

Alfa-helix

Proteins Are Enormously Versatile in Structure The variety of their amino acid side chains, proteins arare remarkably versatile with respect to the type of structures they can form.

Proteins Are Enormously Versatile in Structure Once extreme case is the family of collagen molecules found in the extracelluler space. At the other extreme is the extracellular protein elastin (like rubber)

Proteins Show Different Levels of Structural Organization Though the number of different ways in which even a small protein could fold up is astronomically large, there seems to be some logic in the way in which it occurs.

Proteins Show Different Levels of Structural Organization The three-dimensional structure of a protein can be described in of four different levels of folding, each of which is constructed from the preceding one in hierarchical fashion.

Alternate nomenclature; primary structure, secondary, tertiary, dan quarternary structure.

Relatively Few of the Many Possible Polypeptide Chains Would Be Useful Since each of the 20 amino acids is chemically distinct and each can, in principle, occur at any position in a protein chain, there are 20 X 20 X 20 20 = 160,000 different possible polypeptide chains n amino acids long.

Relatively Few of the Many Possible Polypeptide Chains Would Be Useful For a typical protein length of about 300 amino acids , more than 10 390 different proteins can be made.

New Proteins Often Evolve by Minor Alterations of Old Ones Cells have genetic mechanisms that allow genes to be duplicated and modified in the course of evolution.

New Proteins Often Evolve by Minor Alterations of Old Ones Example; family of proteincleaving (proteolytic) enzymes called serine proteases.

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New Proteins Often Evolve Through the Combination of Different Polypeptide Domains

Once a number of stable protein surfaces have been made in a cell, new surfaces with different binding properties can be generated by the ing of two or more individual proteins together by noncovalent interactions between them.

New Proteins Often Evolve Through the Combination of Different Polypeptide Domains

Juxtaposition of separate protein surfaces, in the course of evolution, could give rise to new binding sites for small moleculess called ligands.

Protein subunits Can Selfassemble into Large Structures in the Cell The same principles that enable several protein domains to associate to form binding sites operate to generate much larger structures in the cell.

A Single Type of Protein subunit Can Interact with Itself to form Geometrically Regular Aggregates

If a protein has a binding site that is complemntary to a region of its own surface, it will assemble spntaneously into an aggregate structure. Exp: symmetrical dimmer

A Single Type of Protein subunit Can Interact with Itself to form Geometrically Regular Aggregates

An example of a helical structure commonly encountered in cells is ten actin filament, which has two helical strands wound around each other and is formed from a single globular protein subunit called actin.

Self-assembling Aggregates Can Include Different Protein Subunits and Nucleic Acids

Many carge cellular structures are constructed from a mixture of different proteins. In some cases, such as viruses and ribosomes, RNA, DNA.

There Are Limits to Self-assembly It is logical to ask whether all cellular structures that are held together by noncovalent bonds are capable of self –assembly.

There Are Limits to Self-assembly Can a mitochondrion, a cilium, a myofibril, or even a whole cell form spontaneously out of a solution of their component macromolecules?

There Are Limits to Self-assembly

No, because for large and complex structures part of the information for assembly is provided by special enzymes and by other cellular proteins that perform the function of jigs or template.

The three-dimensional conformation a protein molecule is determined by its amino acid sequence. Particular folded structures are stabilized by nonco alent interactions between different parts of the polypeptide chain.

Small globular regions known as domains are the modular units from which many proteins are constructed;

Proteins are brought together into aggregates structure by the same forces that determine protein folding. Proteins with binding sites for their own surface can assemble into dimers or larger oligomers, closed rings, spherical shells, or helical polymers.

Mixtures of many different proteins, which can also include structural nucleic acids, can spontaneously assemble into large complex structures in the test tube. However, in many assembly processes irreversible steps occur so that not all structures in the cell are capable of spontaneous reassembly if they are dissociated into their component parts.

PROTEIN FUNCTION The chemical properties of a protein molecule depend almost entirely on its exposed residues, which are able to form different types of weak noncovalent bonds with other molecules.

PROTEIN FUNCTION An effective interaction of a protein molecule with anther molecule (referred to as a ligand) requires that a number of weal bods be formed simultaneously between them. Therefore, the only ligands that can bind tghtly to a protein are those that fit precisely onto its surface.

PROTEIN FUNCTION The region of a protein that associates with a ligand, known as its binding site, usually takes the form of a cavity formed by a specific arrangement of amino acids on the protein surface.

A Protein’s Conformation Determines Its Chemistry Neighboring surface residues on a protein often interact in a way that alters the chemical reactivity of selected amino aced side chains.

A Protein’s Conformation Determines Its Chemistry First, neighboring parts of the polypeptide chain may interact in a way that restricts the access of water molecules to other parts of the protein surface.

A Protein’s Conformation Determines Its Chemistry Second, the clustering of neighboring polar amino acid side chains alters their reactivity. For exp: a number of negatively charged side groups can be forced together against their mutual repulsion by the way that the protein folds.

Substrate Binding Is the First Step in Enzyme Catalysis One of the most important functions of proteins is to act as enzymes that catalyze specific chemical reactions. The ligand in this case is the substrate molecule, and the binding of the substrate to the enzyme is an essential prelude to the chemical reaction.

Substrate Binding Is the First Step in Enzyme Catalysis The way enzymes work; If the concentration of substrate is increase, the rate at which product is formed also increases up to a max. value. This rate is expressed as a turnover number.

Enzymes Accelerate Reaction Rates Without Shifting Equilibria No matter how sophisticated an enzyme becomes, it cannot make the chemical reaction that it catalyzes either more or less energetically favorable.

Many Enzymes Make Reactions Proceed Preferentially in One Direction by Coupling Them to ATP Hydrolysis. The product of each enzyme usually serves as a substrate for another enzyme in the metabolic pathway and is rapidly consumed. Many reactions are driven by being coupled to the hydrolysis of ATP to ADP and inorganic phosphate.

Multienzyme Complexes Help to Increase the Rate of Cell metabolism. Both the efficiency of enzymes in accelerating metabolic reactions and their organization in the cell are crucial to the maintenance of life.

Intracellular Membranes Increase the Rates of Diffusion-limited Reactions. The extensive intracellular membranes of eucaryotic cells act in at least two distinct ways to increase the rates of reaction that would otherwise be limited by the speed diffusion.

Intracellular Membranes Increase the Rates of Diffusion-limited Reactions. First, .membranes can segregate certain substrates and all the enzyme that act on them into the same membrane-limited compartment, as in the mitochondrion or the cell nucleus.

Intracellular Membranes Increase the Rates of Diffusion-limited Reactions. Second, membranes can restrict the diffusion of reactants to the two dimensions of the membrane itself so that enzymes and their substrates are much more likely to collide with each other than if they were diffusing in three dimensions.

Protein Molecules Can Reversibly Change Their Shape Because the mechanics of cellular life generally demand stable molecular structure, evolutionary pressures have worked against the ability of polypeptides to change randomly from one conformation to another.

Protein Molecules Can Reversibly Change Their Shape Protein with this property are known as allosteric proteins. Each distinct conformation of an allosteric protein has a somewhat different surface and thus a different ability to interact with other molecules.

Allosteric Protein Are Involved in Metabolic Regulation Allosteric protein are essential to the regulation that control the flux through a metabolic pathway. Enzyme, that act early in a pathway are almost always allosteric proteins that can exist in two different conformations.

Allosteric Protein Are Vital for Cell Signaling Allosteric protein such as those involved in regulation have at least two binding sites, one for the enzyme substrate and one or more for regulatory ligands.

Protein Can Be Pushed or Pulled into Different Shape All of the directed movements in cells depend on forces generated by proteins. Consider an allosteric protein that can adopt two alternative conformations; a low energy form C (inactive) and a high-energy form C* (active)

Protein Can Be Pushed or Pulled into Different Shape An input of chemical energy can be used to “push” conformation C to the active form C* in much less reversible manner. Common: a phosphate group from ATP to a serine, threonine, or tyrosine residue in the protein, forming a covalent linkage.

Energy-driven Changes in Protein Conformations Can Do Useful Work Suppose a protein is required to “walk” a long a narrow thread, such as a microtubule or a DNA molecule. DNA helicase, a protein that plays an essential part in DNA replication

ATP-driven Membrane-bound Allosteric Proteins Can Act as Pumps Allosteric proteins can use the energy of ATP hydrolysis to do other forms of work, such as pumping specific ions into or out of the cell. Na, K , ATPase

Protein Molecules Can Harness Ion Gradients to Do Useful Work The large Na gradient across the plasma membrane generated by the Na, K, ATPase is used to drive other plasmamembrane-bound protein pumps that transport glucose or amino acids into the cell. “ping-pong” pump oscilates

Summary • The biological function of a protein depends on the detailed chemical properties of its surface. • Binding sites are formed as surface cavities in which precisely positioned amino acid chains are brought together by protein folding. • Enzymes catalyze chemical changes in bound substrate molecules, often employing small, tightly bound coenzyme molecules to extend the range of their reactions.

Summary • Allosteric proteins reversibly change their shape when ligands bind to their surface. • The changes produced by one ligand can affect the binding of a second ligand, thereby providing a mechanism for regulating various cell processes. • Such changes in protein shape are often driven in an unidirectional manner by the expenditure of chemical energy.