Presentation on theme: " Super secondary Structures (Motifs); The term motif refers to a set of contiguous secondary structure elements that either have a particular functional."— Presentation transcript:
Super secondary Structures (Motifs); The term motif refers to a set of contiguous secondary structure elements that either have a particular functional significance or define a portion of an independently folded domain. Or small, distnct, specific aggregates of secondary structures. Super Secondary structure composition, e.g. all , all , segregated + , mixed / .
Definition; It refers to the folding of the polypeptide chain into a compact three dimensional structure, or it refers to the spatial arrangement of amino acid residues which are far apart in the amino acid linear sequence, and how they interact with each other, leading to the folding of the polypeptide chain into a 3 dimensional structure. Example Myoglobin. Stabilizing bonds; Include a large number of weak non-covalent bonds such as, Hydrogen bonds, ionic bnds, hydrophobic interactions, vander-Wall forces. Tertiary structures usually obtain a globular shape. The three dimensional structure of a protein is determined by its primary structure (its amino acid sequence in the polypeptide chain) which determined by it’s specific coding gene.
The interactions of the R groups give a protein its specific three- dimensional tertiary structure. 5
Proteins that are composed of more than one polypeptide chain (subunit)show a fourth level of protein structure Which is the quaternary structure. Definition ; It refers to the manner in which individual polypeptide chains interact or fit with each other to form an oligomeric protein molecule which resembles the functional unit. Stabilizing bonds; Include a large number of weak non-covalent bonds such as, Hydrogen bonds, ionic bnds, hydrophobic interactions, vander-Wall forces. The subunits in the quaternary structure can be identical or different in structure. Two kinds of quaternary structures: a) homo (dimer, trimer,….ect) protein, when the subunits are identical. b) hetero (dimer, trimer ….ect)protein when the subunits are different. The subunits may function independently or cooperatively as in Hb.
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.
It is located in the muscle tissue and is responsible for its brown color. Its function is to store and transport oxygen in the skeletal muscles. It is a relatively small protein made up of a single polypeptide chain that contains 153 amino acid residues. It contains a heme group (which is a prosthetic group consisting of a protoporphyrin organic ring and a central iron atom). It is the heme group which is responsible for the oxygen binding capacity of Myoglobin. Myoglobin is very similar to Hemoglobin in both its function and structure ( since both are capable of oxygenation and deoxygenation). Myoglobin is an extremely compact molecule(in its interior there is room for only 4 H 2 O molecules) The backbone of the polypeptide chain is made up of 8 segments of α-helical structures, the largest segment has 23 a.a while the shortest 7 a.a residues.
Thus 70% of the main polypeptide chain in myoglobin is involved in α-helical structures. The rest of the polypeptide chain is loops or bends between the α-helical segments. The non-polar amino acids are arranged in the interior (e.g Leu, Val, Phe)thus producing a hydrophobic interior. The polar or charged amino acids( e.g Glu, Asp, ) are located on the outer surface, except for 2 His residues which are in the interior since they play a critical role in binding iron. The pro residues and other non-helical a.a residues occur only at the bends that link the α-helical segments together.
The heme group of myoglobin sits in a cleft in the interior of the molecule lined with non-polar a.a (except for the 2 His). There are 2 His in the interior of the myoglobin molecule, the proximal His which binds directly to the iron atom, the second His does not interact directly with the heme group, but helps stabilize the binding of the O 2 to the ferrous atom.
Hemoglobin is an oligomeric protein which is composed of 4 polypeptide chains. Each poypeptide chain has a heme prosthetic group attached to it in which the iron atom is in the fe 2+ state. The protein part of hemoglobin is called globin which consists of 2 α chains (141 amino acid residue) and 2β chains (146 amino acid residues). It is roughly spherical with a 5.5 nm diameter. The single polypeptide chain (subunit) resembles in its structure the structure of myoglobin, thus the α and β chains contain several segments of α-helix separated by bends. Each heme is partially burried in a hydrophobic pocket lined with non-polar amino acids. The heme group is bound to its poypeptide chain through a coordination bond of the iron atom to the R- group of the proximal His residue.
Structure of the heme group ; It consists of a complex organic ring structure (protoporphyrin) which is a tetrapyrrol ring linked by four methene bridges ( =CH groups). It contains methyl, vinyl,propionic acid groups attached to the pyrrol rings. The non-polar vinyl group is burried in the hydrophobic interior while the hydrophilic groups of the propionic acid projects out of the pocket to the outside. The iron atom has 6 coordination bonds four in the plane of the portophyrin ring and attached to it by binding to the 4 central nitrogen atoms, the two remaining coordination bonds are perpendicular to the heme plane where one will bind to nitrogen atom of the proximal His residue and the other will bind the O 2 molecule.
Hemoglobin undergoes conformational changes on binding oxygen; The Hemoglobin molecule can presume two major conformations, the R-state (relaxed state), and the T-state (tensed state). Although Oxygen can bind to both conformations but it shows a significantly higher affinity towards the R-state. The T-state is stabilized by a number of ionic bonds between the (α 1 β 1 ) and (α 2 β 2 ) dimers. The binding of oxygen to a hemoglobin subunit in the T-state triggers a conformational change to the favored R-state, through the breaking of some of the ionic bonds with the formation of some new ones.
Oxygen binding to hemoglobin; A plot of % saturation of hemoglobin against pO 2 (oxygen partial pressure) is sigmoidal, whereas that of myoglobin is hyperbolic. This sigmoidal curve of hemoglobin means that hemoglobin has relatively low affinity for binding the first one or two O 2 molecules but once they are bound the binding of subsequent oxygen molecules is increased (cooperative O 2 binding). Conversly the loss of one O 2 molecule from the fully oxygenated Hb Causes the rest to dissociate more easily when pO 2 is decreased. The myoglobin hyperbolic curve shows that myoglobin has a higher affinity towards O 2 compared to Hb. A protein with high affinity to O 2 will bind efficiently in the lungs but will not easily release it in the tissues. Thus myoglobin cannot carry O 2 from the lungs to the tissues as Hb.
On the other hand the lower affinity seen in Hb suits its function since it enables to bind O 2 efficiently in the lungs where the pO 2 Is high and release the O 2 easily at the tissues where the pO 2 is decreased.
The Bohr Effect; The effect of pH on the O 2 - Hb equilibrium is called the Bohr effect ; HHb + O 2 HbO 2 + H +. When hb is oxygenated it ionizes to free one H + for each O 2 bound as seen in the equation. Since the reaction is a reversible reaction, increasing the [ H + ] will cause the equilibrium to shift to the left releasing the O 2. The relationship between pH and the Hb %Oxygen saturation is directly related. This pH effect and the sigmoidal property of Hb allows it to carry O 2 Efficiently. In the lungs where the partial pressure of O 2 is high approximately 100 mm Hg, and the pH is also high 7.4,the environment favors the binding of O 2.
Whereas at the tissues where the pO 2 is lower and the pH is lower deoxygenation of Hb is favored.