Question

4 levels of proteins? Describe with detail the molecular configuration of each level. What molecular and environmental items are required to ensure that proteins are functional?

Answer 1

1. Proteins are polymers formed from sequences of amino acids. The baisc structure of amino acid contains a central carbon atom, amino group (NH3+) at one end, carboxyl group (COO-) at other end and a side chain or R group. This side chain differs in all 20 naturally occuring amino acids. There are four distinct levels of protien structure.

Primary structure: It is the simplest level of protein structure formed of sequence of amino acids in a polypeptide chain. The primary structure mainly consists of peptide bond by which the amino acids are held together in a polypeptide chain. These peptide bonds are formed during protein synthesis. Depending upon the nature of free group at both the ends the two ends of polypeptide chain are referred to as carboxyl terminal (C-terminal) (-COOH)and amino terminal (N-terminal) (-NH2 group). Counting of residues starts from N-terminal as amino group (NH2) is not involved in peptide bond.

Secondary structure: It is the next level of protein structure formed due to interactions between atoms on the side chains. The two main types of secondary structures are alpha helix and beta pleated sheets. These structures are defined by presence of hydrogen bonds formed between the main peptide group (CO-NH). In alpha helix the hydrogen bonds are formed between carbonyl O of one amino acid and the amino H of the fourth amino acid in the polypeptide chain. Due to this bonding the pilypeptide chain forms helix with 3.6 amino acids at each turn of helix. In beta pleated sheets two or more polypeptide chain line up next to each other. Alpha helix is further divided into right handed and left handed alpha helix. The strands of beta pleated sheets may be parallel (i.e their C-terminal and N-terminal are placed in same direction) and antiparallel (i.e. their C-terminal and N-terminal are placed in opposite direction to each other). Most of the proteins contain both alpha helix and beta pleated sheets in structure while other may contain any one type of secondary structure.

Tertiary structure: Tertiary structure refers to 3-dimensional structure of monomeric or multimeric protein. At this level the alpha helix and beta pleated sheets are folded in compact globular structure. Tertiary structure is primarily due to interaction between the R groups of the amino acids. Non-covalent interactions such as hydrogen bonding, ionic bonding, dipole-dipole interactions and london-dispersion forces drive the foldings in tertiary structure. Disulfide bonds and hydrophobic interactions also play an important role in tertiary structure.

Quaternary structure: The last level of protein organisation quaternary structure is a three dimensional structure made up of aggregation of two or more individual polypeptide chains (subunits) that functions as single functional unit (multimeric). The multimeric structure is stabilized by same non-covalent interactions and disulfide bonds as in tertiary structure. Multimers made of identical subunits are referred to with the prefix homo- and those with different subunits as hetero-.

2. The proteins are functional when they are properly folded. If the protein is unfolded or misfolded they become non-functional. To perform their biological funtions, proteins are folded into one or more spatial conformations driven by non-covalent interactions such as hydrogen bonding, ionic interactions, Van der waals forces and hydrophobic interactions. These bondings stabilize protein structure and make them well adapted for their functions. Change in temperature or pH or exposure to chemicals disrupts these interactions which causes protein to lose its three dimensional structure and converting them into unstructures string of amino acids. High temperature increases kinetic energy as a result the molecules vibrate rapidly and violently thus disrupting hydrogen bonds and non-polar hydrophobic interactions. The presence of high salt in protien solution will disturb the local water structure around the protein thus decreasing the tendency of intermolecular hydrogen bonding and affecting protein solubility, binding, stability and crystallization. Denaturation caused by change in pH affects the chemistry of amino acids. Change in pH cause ionizable groups in amino acids to become ionized. A pH change to more acidic or basic condition can induce unfolding of protein.