Familial Abdominal 3 Aortic Aneurysm

12/24/2019 - "Here, we explored the allosteric transition path of dynein involving AAA3 using a coarse-grained structure-based model. "
12/24/2019 - "However, the comprehensive structural perspective of AAA3 in dynein's mechanochemical cycle remains unclear. "
09/19/2008 - "In addition to changes in motility characteristics, AAA3 and AAA4 mutants produce less maximal force than wild-type dynein. "
12/24/2019 - "Therefore, we suggest that AAA3 governs dynein's mechanochemical cycle and motility by controlling the AAA4 and AAA5 domains that further regulate the linker movement and the power stroke formation."
10/25/2021 - "In this study, we found that dynein containing a mutation-blocking ATP hydrolysis at AAA3 can undergo LIS1-independent activation, consistent with our genetic data that the same mutation suppresses the growth defect of the A. nidulans LIS1-deletion mutant. "

09/19/2008 - "Although previous studies have proposed regulatory roles for AAA3 and AAA4, the role of ATP hydrolysis at these sites remains elusive. "
12/24/2019 - "The free energy calculation shows that the linker prefers the straight conformation when AAA3 remains in the ATP-bound condition. "
05/19/2015 - "However, when tension is applied to the linker, ATP binding to AAA3 is sufficient to "open" the gate. "
10/25/2021 - "In this study, we found that dynein containing a mutation-blocking ATP hydrolysis at AAA3 can undergo LIS1-independent activation, consistent with our genetic data that the same mutation suppresses the growth defect of the A. nidulans LIS1-deletion mutant. "
01/01/2023 - "Our analysis shows that in the absence of ATP, all dynein linkers interact with the AAA3/AAA4 domains, indicating that interactions with the adjacent microtubule doublet B-tubule direct dynein orientation. "

10/21/2021 - "These data, along with functional assays of dynein motility and mutagenesis studies, suggest that the compounds inhibit dynein by engaging the regulatory ATPase sites in the AAA3 and AAA4 domains, and not by interacting with dynein's main catalytic site in the AAA1 domain. "
10/25/2021 - "Together, our data suggest that the AAA3 ATPase cycle regulates the coordination between dynein activation and cargo binding as well as the dynamic dynein-LIS1 interaction."
01/01/2015 - "ATPase mutations to AAA3 abolish the ability of dynein to modulate MT release. "
01/01/2015 - "ATPase activity at AAA3 is also essential for robust motility, but its role in dynein's mechanochemical cycle remains unclear. "
11/06/2014 - "Here, we report X-ray and electron microscopy (EM) structures of yeast dynein bound to different ATP analogs, which collectively provide insight into the roles of dynein's two major ATPase sites, AAA1 and AAA3, in the conformational change mechanism. "

01/01/2015 - "Nucleotide hydrolysis at AAA3 lifts this 'MT gate' to allow fast motility. "
01/01/2015 - "Analysis of pausing behavior revealed that AAA3 hydrolyzes nucleotide an order of magnitude more slowly than AAA1, and the two sites do not coordinate. "
11/06/2014 - "In contrast to the role of AAA1 in driving motility, nucleotide transitions in AAA3 gate the transmission of conformational changes between AAA1 and the linker, suggesting that AAA3 acts as a regulatory switch. "
10/25/2021 - "Dynein activation in vivo is regulated by the nucleotide states of its AAA3 domain."
12/24/2019 - "Nucleotide states in AAA3 gate dynein's activity, suggesting that AAA3 acts as a regulatory switch. "

01/01/2015 - "These results suggest that AAA3 acts as a switch that repurposes cytoplasmic dynein for fast cargo transport and MT-anchoring tasks in cells. "
01/01/2015 - "The AAA3 domain of cytoplasmic dynein acts as a switch to facilitate microtubule release."
09/19/2008 - "Here, we have analyzed the single molecule motility properties of yeast cytoplasmic dynein mutants bearing mutations that prevent ATP hydrolysis at AAA3 or AAA4. "

12/24/2019 - "Role of AAA3 Domain in Allosteric Communication of Dynein Motor Proteins."

01/01/2022 - "Other rare variants of 11.1 kb deletions (- 11.1/αα), triplicate α-globin genes (aaa3.7/αα) and rare SNVs have also been thoroughly detected. "

10/21/2021 - "A double Walker B mutation of the AAA3 and AAA4 sites substantially reduces enzyme activity, suggesting that targeting these regulatory domains is sufficient to inhibit dynein. "

05/19/2015 - "Using nucleotide binding and hydrolysis mutants, we show that, although ATP exerts its effects via binding AAA1, ADP effects are mediated by AAA3. "

10/25/2021 - "Our data also suggest that blocking AAA3 ATP hydrolysis allows dynein activation by dynactin without the early endosomal adaptor. "