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      Fundamental Characteristics of AAA+ Protein Family Structure and Function

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      Archaea
      Hindawi Publishing Corporation

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          Abstract

          Many complex cellular events depend on multiprotein complexes known as molecular machines to efficiently couple the energy derived from adenosine triphosphate hydrolysis to the generation of mechanical force. Members of the AAA+ ATPase superfamily (ATPases Associated with various cellular Activities) are critical components of many molecular machines. AAA+ proteins are defined by conserved modules that precisely position the active site elements of two adjacent subunits to catalyze ATP hydrolysis. In many cases, AAA+ proteins form a ring structure that translocates a polymeric substrate through the central channel using specialized loops that project into the central channel. We discuss the major features of AAA+ protein structure and function with an emphasis on pivotal aspects elucidated with archaeal proteins.

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          Most cited references127

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          Structure and mechanism of helicases and nucleic acid translocases.

          Helicases and translocases are a ubiquitous, highly diverse group of proteins that perform an extraordinary variety of functions in cells. Consequently, this review sets out to define a nomenclature for these enzymes based on current knowledge of sequence, structure, and mechanism. Using previous definitions of helicase families as a basis, we delineate six superfamilies of enzymes, with examples of crystal structures where available, and discuss these structures in the context of biochemical data to outline our present understanding of helicase and translocase activity. As a result, each superfamily is subdivided, where appropriate, on the basis of mechanistic understanding, which we hope will provide a framework for classification of new superfamily members as they are discovered and characterized.
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            Structure at 2.8 A resolution of F1-ATPase from bovine heart mitochondria.

            In the crystal structure of bovine mitochondrial F1-ATPase determined at 2.8 A resolution, the three catalytic beta-subunits differ in conformation and in the bound nucleotide. The structure supports a catalytic mechanism in intact ATP synthase in which the three catalytic subunits are in different states of the catalytic cycle at any instant. Interconversion of the states may be achieved by rotation of the alpha 3 beta 3 subassembly relative to an alpha-helical domain of the gamma-subunit.
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              Distantly related sequences in the alpha- and beta-subunits of ATP synthase, myosin, kinases and other ATP-requiring enzymes and a common nucleotide binding fold.

              The alpha- and beta-subunits of membrane-bound ATP synthase complex bind ATP and ADP: beta contributes to catalytic sites, and alpha may be involved in regulation of ATP synthase activity. The sequences of beta-subunits are highly conserved in Escherichia coli and bovine mitochondria. Also alpha and beta are weakly homologous to each other throughout most of their amino acid sequences, suggesting that they have common functions in catalysis. Related sequences in both alpha and beta and in other enzymes that bind ATP or ADP in catalysis, notably myosin, phosphofructokinase, and adenylate kinase, help to identify regions contributing to an adenine nucleotide binding fold in both ATP synthase subunits.
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                Author and article information

                Journal
                Archaea
                Archaea
                ARCHAEA
                Archaea
                Hindawi Publishing Corporation
                1472-3646
                1472-3654
                2016
                14 September 2016
                : 2016
                : 9294307
                Affiliations
                Department of Structural Biology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA
                Author notes

                Academic Editor: Baolei Jia

                Author information
                http://orcid.org/0000-0001-9230-9483
                http://orcid.org/0000-0003-4055-633X
                Article
                10.1155/2016/9294307
                5039278
                27703410
                4ec49665-4be1-4ea2-a2bd-f3e899bfd4f0
                Copyright © 2016 J. M. Miller and E. J. Enemark.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 11 June 2016
                : 21 July 2016
                Funding
                Funded by: ALSAC
                Award ID: R01GM098771
                Categories
                Review Article

                Animal science & Zoology
                Animal science & Zoology

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