Protein folding mechanisms pathways

Methods for protein fragmentation were initially developed to study protein folding mechanisms and pathways [58,59]. Since, their application has been extended towards the elucidation of structural organization in proteins and their evolutionary origins, as well as towards the design of novel two-hybrid systems. 

Guo Z and Thirumalai D 1995 Kinetics of protein folding nucleation mechanism, time scales and pathways Biopolymers 36 83-103... 

Protein trafficking is the transport of proteins to their correct subcellular compartments or to the extracellular space ( secretory pathway ). Endo- and exocytosis describe vesicle budding and fusion at the plasma membrane and are by most authors not included in the term protein trafficking. Protein quality control comprize all cellular mechanisms, monitoring protein folding and detecting aberrant forms. 

To solve the greatest questions of protein folding, however, this gap must be bridged. Obviously, predicted folding pathways and mechanisms axe only meaningful if the physical significance of the model can be established as well. This is also true for the continued development and/or refinement of simplified models for reliable structure predictions. In... 

A pathway analogous to the DsbA-DsbB system was recently shown to operate in the endoplasmic reticulum of eukaryotes (Frand and Kaiser, 1998 1999 Pollard et al., 1998). This pathway includes the membrane-bound protein EROl, which keeps protein disulfide isomerase (PDI) in an oxidized state in vivo. Consequently, PDI plays a role somewhat similar to that of DsbAin catalyzing the formation of disulfide bonds during the folding of secreted proteins. The mechanisms driving oxidative protein folding in eukaryotes are described in more detail in another chapter in this volume. 

An instructive parallel may be drawn between the identification and characterization of electron transfer pathways and the identification and characterization of protein folding pathways (199-202). In the simplest cases, both processes are intramolecular and involve a transition between an initial and final state. An advantage to understanding electron transfer pathways is that both states are structurally ordered, whereas protein folding converts a disordered initial state into a structurally ordered final state. In both situations, a number of mechanisms for this transition have been envisioned, ranging from a few dominant pathways to many, different pathways. The challenge in both cases is to develop experimental approaches that will define and enumerate the number of pathways. 

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