title: Actinous enigma or enigmatic actin: Folding, structure, and functions of the most abundant eukaryotic protein.
abstract: Being the most abundant protein of the eukaryotic cell, actin continues to keep its secrets for more than 60 years. Everything about this protein, its structure, functions, and folding, is mysteriously counterintuitive, and this review represents an attempt to solve some of the riddles and conundrums commonly found in the field of actin research. In fact, actin is a promiscuous binder with a wide spectrum of biological activities. It can exist in at least three structural forms, globular, fibrillar, and inactive (G-, F-, and I-actin, respectively). G-actin represents a thermodynamically instable, quasi-stationary state, which is formed in vivo as a result of the energy-intensive, complex posttranslational folding events controlled and driven by cellular folding machinery. The G-actin structure is dependent on the ATP and Mg2+binding (which in vitro is typically substituted by Ca2+) and protein is easily converted to the I-actin by the removal of metal ions and by action of various denaturing agents (pH, temperature, and chemical denaturants). I-actin cannot be converted back to the G-form. Foldable and "natively folded" forms of actin are always involved in interactions either with the specific protein partners, such as Hsp70 chaperone, prefoldin, and the CCT chaperonin during the actin folding in vivo or with Mg2+and ATP as it takes place in the G-form. We emphasize that the solutions for the mysteries of actin multifunctionality, multistructurality, and trapped unfolding can be found in the quasi-stationary nature of this enigmatic protein, which clearly possesses many features attributed to both globular and intrinsically disordered proteins.
authors.affiliation: Laboratory of structural dynamics, stability, and folding of proteins; Institute of Cytology; Russian Academy of Sciences; St. Petersburg, Russia.
authors.forename: Olga I
authors.initials: OI
authors.lastname: Povarova
authors.affiliation: Laboratory of structural dynamics, stability, and folding of proteins; Institute of Cytology; Russian Academy of Sciences; St. Petersburg, Russia; Department of Molecular Medicine and USF Health Byrd Alzheimer's Research Institute; Morsani College of Medicine; University of South Florida; Tampa, FL USA; Institute for Biological Instrumentation; Russian Academy of Sciences; Pushchino, Russia; Biology Department; Faculty of Science; King Abdulaziz University; Jeddah, Kingdom of Saudi Arabia.
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Uversky
authors.affiliation: Laboratory of structural dynamics, stability, and folding of proteins; Institute of Cytology; Russian Academy of Sciences; St. Petersburg, Russia; St. Petersburg State Polytechnical University; St. Petersburg, Russia.
authors.forename: Irina M
authors.initials: IM
authors.lastname: Kuznetsova
authors.affiliation: Laboratory of structural dynamics, stability, and folding of proteins; Institute of Cytology; Russian Academy of Sciences; St. Petersburg, Russia; St. Petersburg State Polytechnical University; St. Petersburg, Russia.
authors.forename: Konstantin K
authors.initials: KK
authors.lastname: Turoverov
keywords: actin; hub protein; microfilaments; multifunctional protein; signal transduction