7eb6: Difference between revisions
New page: '''Unreleased structure''' The entry 7eb6 is ON HOLD Authors: Cheng, N., Zhang, H., Zhang, S., Ma, X., Meng, G. Description: Crystal structure of GTP-binding protein-like domain of AGA... |
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The | ==Crystal structure of GTP-binding protein-like domain of AGAP1== | ||
<StructureSection load='7eb6' size='340' side='right'caption='[[7eb6]], [[Resolution|resolution]] 3.01Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7eb6]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7EB6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7EB6 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.014Å</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7eb6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7eb6 OCA], [https://pdbe.org/7eb6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7eb6 RCSB], [https://www.ebi.ac.uk/pdbsum/7eb6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7eb6 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/AGAP1_HUMAN AGAP1_HUMAN] GTPase-activating protein for ARF1 and, to a lesser extent, ARF5. Directly and specifically regulates the adapter protein 3 (AP-3)-dependent trafficking of proteins in the endosomal-lysosomal system.<ref>PMID:12640130</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
AGAP1 is often considered to regulate membrane trafficking, protein transport and actin cytoskeleton dynamics. Recent studies have shown that aberrant expression of AGAP1 is associated with many diseases, including neurodevelopmental disorders and acute lymphoblastic leukemia. It has been proposed that the GTP-binding protein-like domain (GLD) is involved in the binding of cofactors and thus regulates the catalytic activity of AGAP1. To obtain a better understanding of the pathogenic mechanism underpinning AGAP1-related diseases, it is essential to obtain structural information. Here, the GLD (residues 70-235) of AGAP1 was overexpressed in Escherichia coli BL21 (DE3) cells. Affinity and gel-filtration chromatography were used to obtain AGAP1GLD with high purity for crystallization. Using the hanging-drop vapor-diffusion method with the protein at a final concentration of 20 mg ml(-1), AGAP1GLD protein crystals of suitable size were obtained. The crystals were found to diffract to 3.0 A resolution and belonged to space group I4, with unit-cell parameters a = 100.39, b = 100.39, c = 48.08 A. The structure of AGAP1GLD exhibits the highly conserved functional G1-G5 loops and is generally similar to other characterized ADP-ribosylation factor (Arf) GTPase-activating proteins (GAPs), implying an analogous function to Arf GAPs. Additionally, this study indicates that AGAP1 could be classified as a type of NTPase, the activity of which might be regulated by protein partners or by its other domains. Taken together, these results provide insight into the regulatory mechanisms of AGAP1 in cell signaling. | |||
Crystal structure of the GTP-binding protein-like domain of AGAP1.,Cheng N, Zhang H, Zhang S, Ma X, Meng G Acta Crystallogr F Struct Biol Commun. 2021 Apr 1;77(Pt 4):105-112. doi:, 10.1107/S2053230X21003150. Epub 2021 Mar 31. PMID:33830075<ref>PMID:33830075</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 7eb6" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: Meng | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Cheng N]] | |||
[[Category: Ma X]] | |||
[[Category: Meng G]] | |||
[[Category: Zhang H]] | |||
[[Category: Zhang S]] | |||
Latest revision as of 19:49, 29 November 2023
Crystal structure of GTP-binding protein-like domain of AGAP1Crystal structure of GTP-binding protein-like domain of AGAP1
Structural highlights
FunctionAGAP1_HUMAN GTPase-activating protein for ARF1 and, to a lesser extent, ARF5. Directly and specifically regulates the adapter protein 3 (AP-3)-dependent trafficking of proteins in the endosomal-lysosomal system.[1] Publication Abstract from PubMedAGAP1 is often considered to regulate membrane trafficking, protein transport and actin cytoskeleton dynamics. Recent studies have shown that aberrant expression of AGAP1 is associated with many diseases, including neurodevelopmental disorders and acute lymphoblastic leukemia. It has been proposed that the GTP-binding protein-like domain (GLD) is involved in the binding of cofactors and thus regulates the catalytic activity of AGAP1. To obtain a better understanding of the pathogenic mechanism underpinning AGAP1-related diseases, it is essential to obtain structural information. Here, the GLD (residues 70-235) of AGAP1 was overexpressed in Escherichia coli BL21 (DE3) cells. Affinity and gel-filtration chromatography were used to obtain AGAP1GLD with high purity for crystallization. Using the hanging-drop vapor-diffusion method with the protein at a final concentration of 20 mg ml(-1), AGAP1GLD protein crystals of suitable size were obtained. The crystals were found to diffract to 3.0 A resolution and belonged to space group I4, with unit-cell parameters a = 100.39, b = 100.39, c = 48.08 A. The structure of AGAP1GLD exhibits the highly conserved functional G1-G5 loops and is generally similar to other characterized ADP-ribosylation factor (Arf) GTPase-activating proteins (GAPs), implying an analogous function to Arf GAPs. Additionally, this study indicates that AGAP1 could be classified as a type of NTPase, the activity of which might be regulated by protein partners or by its other domains. Taken together, these results provide insight into the regulatory mechanisms of AGAP1 in cell signaling. Crystal structure of the GTP-binding protein-like domain of AGAP1.,Cheng N, Zhang H, Zhang S, Ma X, Meng G Acta Crystallogr F Struct Biol Commun. 2021 Apr 1;77(Pt 4):105-112. doi:, 10.1107/S2053230X21003150. Epub 2021 Mar 31. PMID:33830075[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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