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Accueil du site → Doctorat → Inde → 2007 → Molecular characterization of genes involved in drought responsive proteome of Legume

Jawaharlal Nehru University (2007)

Molecular characterization of genes involved in drought responsive proteome of Legume

Bhushan, Deepti

Titre : Molecular characterization of genes involved in drought responsive proteome of Legume

Auteur : Bhushan, Deepti

Université de soutenance : Jawaharlal Nehru University

Grade : Doctor of Philosophy (PhD) 2007

Sommaire partiel
Sickle cell anemia is the consequence of a point mutation (Glu6 Val) at the sixth position in the 13-chain of the hemoglobin (Hb) molecule. The replacement of a charged residue with a hydrophobic one ·causes the deoxygenated protein to polymerize into long and multi-stranded helical fibers that are believed to be the principle cause of the sickle cell disease. Biophysical studies have revealed that the basic unit of the sickle hemoglobin (HbS) fiber consists of 14 filaments made out of a double-stranded arrangement of Hb molecules similar to those found in the crystals of HbS. The fiber architecture is stabilized by two kinds of interactions, namely, intra-double strand (axial and lateral) and inter-double strand. While intradouble strand contacts of the crystal are preserved in the fiber, the inter-double strand contacts are unique to the fiber. The identity of many of these intermolecular contact residues are known from solution polymerization experiments of natural variants or mutant hemoglobins and HbS crystal structure. However, our present knowledge of intermolecular interaction in the HbS fiber is largely limited to the identity of the contact residues with little information on the interaction strength of individual contact residues. The effect of simultaneous perturbation of contact residues have been experimentally demonstrated for some sites but the mechanistic basis of additive or non-additive coupling between these interacting sites is far from clear. HbS fiber formation is a complex process that requires specific contacts, and presumably intricate interplay between several residues from both, a and 13, chains of the tetramer. Besides, the polymerization occurs only on in the deoxy state (’T’ state) of the HbS suggesting that quaternary conformational events are detrimental to the polymerization process. However studies of quaternary structure vis a vis HbS polymerization has not been carried out though the impact of quaternary structur-al constrains has been extensively analysed in the context of deciphering the mechanistic imperatives of hemoglobin allostery. In as much as the HbS polymerization is triggered by the acquisition of T structure, it is legitimate to conceive that perturbation of this quaternary state may have perceptible influence on kinetics and/or equilibrium ofthe polymerization reaction.

Mots clés : Genes Drought responsive legume proteome

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