Abstract:
Gene encodes linear sequence of nucleotides that specify amino acids attached
through peptide bond in a head to tail fashion. Christian B. Anfinson (1954)
postulated that information for a protein to fold in a three-dimensional structure
provided from a one dimensional amino acid sequence. A protein has to fold
properly to attain correct minimal-energy configuration to arrive at its native,
functional form. This process occurs in micro- to nano- seconds. Levinthal
(1968) stated that protein rapidly folds through nearby amino acids interaction,
thus limiting the available conformational space. Protein folding follows a
funnel-shaped energy landscape to attain the minimal energy and most stable
confirmation. Often protein folds in a co-translational manner, while others in
specific compartments like ER fold after trafficking and translocation through
its membrane. Protein misfolding is one of the common events occurring in a cell. Protein
misfolding occurs when a protein cannot fold into its native form primarily due
to aggregation propensity of amino acid sequences. Molecular chaperones help the proteins that have difficulty in attaining their native state. Often
accumulations of misfolded proteins are checked by cellular proteastatic
machineries. Due to disturbance in the fine balance between generation and
degradation of misfolded proteins, it starts building up and burdens the protein
quality control system which eventually reduces its efficacy. Misfolded proteins
convert to toxic aggregates by the widely accepted “Nuclear growth model”
(Vendruscolo M et al., 2011).
