Topic
AAA proteins
About: AAA proteins is a research topic. Over the lifetime, 823 publications have been published within this topic receiving 54186 citations. The topic is also known as: AAA+ ATPase domain, protein family & IPR003593.
Papers published on a yearly basis
Papers
TL;DR: Whole-genome analysis indicates that this class of proteins is ancient and has undergone considerable functional divergence prior to the emergence of the major divisions of life.
Abstract: Using a combination of computer methods for iterative database searches and multiple sequence alignment, we show that protein sequences related to the AAA family of ATPases are far more prevalent than reported previously. Among these are regulatory components of Lon and Clp proteases, proteins involved in DNA replication, recombination, and restriction (including subunits of the origin recognition complex, replication factor C proteins, MCM DNA-licensing factors and the bacterial DnaA, RuvB, and McrB proteins), prokaryotic NtrC-related transcription regulators, the Bacillus sporulation protein SpoVJ, Mg2+, and Co2+ chelatases, the Halobacterium GvpN gas vesicle synthesis protein, dynein motor proteins, TorsinA, and Rubisco activase. Alignment of these sequences, in light of the structures of the clamp loader delta' subunit of Escherichia coli DNA polymerase III and the hexamerization component of N-ethylmaleimide-sensitive fusion protein, provides structural and mechanistic insights into these proteins, collectively designated the AAA+ class. Whole-genome analysis indicates that this class is ancient and has undergone considerable functional divergence prior to the emergence of the major divisions of life. These proteins often perform chaperone-like functions that assist in the assembly, operation, or disassembly of protein complexes. The hexameric architecture often associated with this class can provide a hole through which DNA or RNA can be thread; this may be important for assembly or remodeling of DNA-protein complexes.
1,947 citations
TL;DR: The structural organization of AAA+ proteins, the conformational changes they undergo, the range of different reactions they catalyse, and the diseases associated with their dysfunction are reviewed.
Abstract: The AAA+ (ATPases associated with various cellular activities) family is a large and functionally diverse group of enzymes that are able to induce conformational changes in a wide range of substrate proteins. The family's defining feature is a structurally conserved ATPase domain that assembles into oligomeric rings and undergoes conformational changes during cycles of nucleotide binding and hydrolysis. Here, we review the structural organization of AAA+ proteins, the conformational changes they undergo, the range of different reactions they catalyse, and the diseases associated with their dysfunction.
1,265 citations
TL;DR: The AAA+ class appears to have undergone an early radiation into the clamp-loader, DnaA/Orc/Cdc6, classic AAA, and "pre-sensor 1 beta-hairpin" (PS1BH) clades and may provide new leads for investigating the biology of AAA+ ATPases.
851 citations
TL;DR: The critical features of theAAA+ domain are described, current knowledge of how this versatile element is incorporated into larger assemblies is summarized, and specific adaptations of the AAA+ fold are discussed that allow complex molecular manipulations to be carried out for a highly diverse set of macromolecular targets.
Abstract: Complex cellular events commonly depend on the activity of molecular "machines" that efficiently couple enzymatic and regulatory functions within a multiprotein assembly. An essential and expanding subset of these assemblies comprises proteins of the ATPases associated with diverse cellular activities (AAA+) family. The defining feature of AAA+ proteins is a structurally conserved ATP-binding module that oligomerizes into active arrays. ATP binding and hydrolysis events at the interface of neighboring subunits drive conformational changes within the AAA+ assembly that direct translocation or remodeling of target substrates. In this review, we describe the critical features of the AAA+ domain, summarize our current knowledge of how this versatile element is incorporated into larger assemblies, and discuss specific adaptations of the AAA+ fold that allow complex molecular manipulations to be carried out for a highly diverse set of macromolecular targets.
834 citations
TL;DR: These findings extend the functional relevance of p97 to lysosomal degradation and reveal a surprising dual role in protecting cells from protein stress and ensuring genome stability during proliferation.
Abstract: The ATP-driven chaperone valosin-containing protein (VCP)/p97 governs critical steps in ubiquitin-dependent protein quality control and intracellular signalling pathways. It cooperates with diverse partner proteins to help process ubiquitin-labelled proteins for recycling or degradation by the proteasome in many cellular contexts. Recent studies have uncovered unexpected cellular functions for p97 in autophagy, endosomal sorting and regulating protein degradation at the outer mitochondrial membrane, and elucidated a role for p97 in key chromatin-associated processes. These findings extend the functional relevance of p97 to lysosomal degradation and reveal a surprising dual role in protecting cells from protein stress and ensuring genome stability during proliferation.
823 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2025 | 14 |
| 2024 | 18 |
| 2023 | 39 |
| 2022 | 77 |
| 2021 | 34 |
| 2020 | 40 |