Supersecondary structures

Supersecondary structures motifs motifs or folds, are particularly stable arrangements of several elements of the secondary structure. Supersecondary structures are usually produced by packing side chains from adjacent secondary structural elements close to each other.

Rules for secondary structure. Hydrophobic side groups must be buried inside the folds, therefore, layers must be created (   ).  -helix and  -sheet, if occur together, are found in different structural layers. Adjacent polypeptide segments are stacked together. Connections between secondary structures do not form knots. The  -sheet is the most stable.

Motif Secondary structure composition, e.g. all , all , segregated  + , mixed  /  Motif = small, specific combinations of secondary structure elements, e.g.  -  -  loop

Supersecodary Structures (Motifs)

Serum albuminFerritin α-amylase inhibitor Immunoglobulin Pilin

Tertiary protein structure Secondary structures fold and pack together to form tertiary structure – Usually globular shape Tertiary structure stabilised by bonds between R groups (i.e. side chains) Intracellular protein tertiary structures mostly held together by weak forces. Extracellular tertiary structures stabilised by disulfide (covalent) bonds.

Three-dimensional structure of proteins Three-dimensional structure of proteins is determined by it amino acid sequence. Function of the protein depends on its structure. Each protein has a unique or nearly unique structure. Non-covalent interactions are the most important forces stabilizing the three dimensional structure of the protein. There common structural patterns in vast protein architecture. Native structure is the natural 3-dimensional structure of a protein.

Domains Domains are the fundamental functional and three- dimensional structural units of polypeptides Polypeptide chains that are greater than 200 amino acids in length generally consist of two or more domains The core of a domain is built from combinations of supersecondary structural elements (motifs) Folding of the peptide chain within a domain usually occurs independently of folding in other domains Therefore, each domain has the characteristics of a small, compact globular protein that is structurally independent of the other domains in the polypeptide chain.

Interactions stabilizing tertiary structure : 1.Disulfide bonds: These strong, covalent bonds help stabilize the structure of proteins, and prevent them from becoming denatured in the extracellular environment. 2.Hydrophobic interactions 3.Hydrogen bonds 4. Ionic interactions

Tertiary structure - disulfide bond – Covalent bond between sulfur atoms on two cysteine amino acids

H bonds weak allowing to be broken and reformed easily – Allows structural change produces ‘functional’ molecules Hydrogen bond Tertiary structure - H bond

Ions on R groups form salt bridges through ionic bonds

Tertiary structure - hydrophobic forces Close attraction of non-polar R groups through dispersion forces Very weak but collective interactions over large area stabilise structure Repel polar and charged molecules/particles

Tertiary Structure

22 Tertiary Structure The interactions of the R groups give a protein its specific three- dimensional tertiary structure.

Tertiary Structure non-linear 3 dimensional global but restricted to the amino acid polymer formed and stabilized by hydrogen bonding, covalent (e.g. disulfide) bonding, hydrophobic packing toward core and hydrophilic exposure to solvent A globular amino acid polymer folded and compacted is somewhat functional (catalytic) and energetically favorable  interaction!

Quaternary Structure of Proteins  Many proteins consist of a single polypeptide chain, and are defined as monomeric proteins.  others may consist of two or more polypeptide chains that may be structurally identical or totally unrelated.  The arrangement of these polypeptide subunits is called the quaternary structure of the protein.

26 Quaternary Structure of Proteins The biological function of some molecules is determined by multiple polypeptide chains – multimeric proteins Two kinds of quaternary structures: both are multi-subunit proteins. Homotypic: association between identical polypeptide chains. Heterotypic: interactions between subunits of very different structures. The interactions within multimers is the same as that found in tertiary and secondary structures

Quarternary Structure This structure for proteins that have more than one polypeptide chains. It is the arrangement of protein subunits (protein that has more than one polypeptide chain) in three dimensional complex. The interaction between subunits are stabilized by: hydrogen bonds electrostatic bonds hydrophobic bonds e.g. of proteins having quaternary structure: Lactate dehydrogenase enzyme: (4 subunits), hemoglobin (4 subunits)

30 Summary of Structural Levels