Molecular Basis for Cooperative Binding of Anionic Phospholipids to the PH Domain of the Arf GAP ASAP1

Jian, Xiaoying; Tang, Wai Kwong; Zhai, Peng; Roy, Nirmolendu; Luo, Ruibai; Gruschus, James M.; Yohe, Marielle E.; Chen, Pei-Wen; Li, Yifei; Byrd, R. Andrew; Xia, Di; Randazzo, Paul A.

doi:10.1016/j.str.2015.08.008

Cited by 59 publications

(107 citation statements)

References 60 publications

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“…54,55 Cooperative binding of ligands controls activity of the Arf GAP ASAP1. 23 Figure 2. The cycle of GDP for GTP exchange and GTP hydrolysis.…”

Section: Introductionmentioning

confidence: 99%

“…76,77 All 4 subtypes of Arf GAPs may be allosterically regulated. 23,54,76,78 ASAP1 has been the most extensively examined Arf GAP and will be discussed here.…”

Section: Introductionmentioning

confidence: 99%

“…Lipid binding to the PH domain of ASAP1 stimulates GAP activity approximately 10,000-fold. 23,55,100,101 Like Grp1, ASAP1 has at least 2 behaviors that are examples of allosterism. The first is binding to 2 phospholipids cooperatively.…”

mentioning

confidence: 99%

“…While ASAP1 constructs consisting of the PH and Arf GAP domains have detectable activity with membrane-bound Arf, the activity is enhanced 15-fold in the presence of PS, and enhanced 1,500-fold further with the addition of PtdIns(4,5)P 2 . 23 This suggests that lipid binding plays some role orienting the PH and, consequently the catalytic GAP domain, at the membrane such that its interaction with Arf favors GTP hydrolysis. In line with this idea is the structural reorganization seen for the b1/ b2 loop upon binding the 2 lipids, with the exposed isoleucine likely favoring additional membrane interaction affecting the orientation of the PH domain at the membrane.…”

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confidence: 99%

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Allosteric properties of PH domains in Arf regulatory proteins

et al. 2016

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Pleckstrin Homology (PH) domains bind phospholipids and proteins. They are critical regulatory elements of a number enzymes including guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs) for Ras-superfamily guanine nucleotide binding proteins such as ADP-ribosylation factors (Arfs). Recent studies have indicated that many PH domains may bind more than one ligand cooperatively. Here we discuss the molecular basis of PH domain-dependent allosteric behavior of 2 ADPribosylation factor exchange factors, Grp1 and Brag2, cooperative binding of ligands to the PH domains of Grp1 and the Arf GTPase-activating protein, ASAP1, and the consequences for activity of the associated catalytic domains.

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“…54,55 Cooperative binding of ligands controls activity of the Arf GAP ASAP1. 23 Figure 2. The cycle of GDP for GTP exchange and GTP hydrolysis.…”

Section: Introductionmentioning

confidence: 99%

“…76,77 All 4 subtypes of Arf GAPs may be allosterically regulated. 23,54,76,78 ASAP1 has been the most extensively examined Arf GAP and will be discussed here.…”

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Allosteric properties of PH domains in Arf regulatory proteins

et al. 2016

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“…PI(4,5)P2 has been found to be important for both ASAP1 and NM2 function. PI (4,5)P2 binding to the PH domain of ASAP1 activates Arf GAP activity of ASAP1, [43][44][45][46] possibly through inducing a conformational change that increases the affinity for the substrates Arf1 and Arf5. Arf3 and Arf4 have not been examined.…”

Section: Asap1 and Nonmuscle Myosin 2a (Nm2a)mentioning

confidence: 99%

Arf GAPs and molecular motors

et al. 2017

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Arf GTPase-activating proteins (Arf GAPs) were first identified as regulators of the small GTP-binding proteins ADP-ribosylation factors (Arfs). The Arf GAPs are a large family of proteins in metazoans, outnumbering the Arfs that they regulate. The members of the Arf GAP family have complex domain structures and some have been implicated in particular cellular functions, such as cell migration, or with particular pathologies, such as tumor invasion and metastasis. The specific effects of Arfs sometimes depend on the Arf GAP involved in their regulation. These observations have led to speculation that the Arf GAPs themselves may affect cellular activities in capacities beyond the regulation of Arfs. Recently, 2 Arf GAPs, ASAP1 and AGAP1, have been found to bind directly to and influence the activity of myosins and kinesins, motor proteins associated with filamentous actin and microtubules, respectively. The Arf GAP-motor protein interaction is critical for cellular behaviors involving the actin cytoskeleton and microtubules, such as cell migration and other cell movements. Arfs, then, may function with molecular motors through Arf GAPs to regulate microtubule and actin remodeling.

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In vitro reconstitution of small GTPase regulation

et al. 2022

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Small GTPases play essential roles in the organization of eukaryotic cells. In recent years, it has become clear that their intracellular functions result from intricate biochemical networks of the GTPase and their regulators that dynamically bind to a membrane surface. Due to the inherent complexities of their interactions, however, revealing the underlying mechanisms of action is often difficult to achieve from in vivo studies. This review summarizes in vitro reconstitution approaches developed to obtain a better mechanistic understanding of how small GTPase activities are regulated in space and time.

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Molecular Basis for Cooperative Binding of Anionic Phospholipids to the PH Domain of the Arf GAP ASAP1

Cited by 59 publications

References 60 publications

Allosteric properties of PH domains in Arf regulatory proteins

Allosteric properties of PH domains in Arf regulatory proteins

Arf GAPs and molecular motors

In vitro reconstitution of small GTPase regulation

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