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Crystal structures of the scaffolding protein LGN reveal the general mechanism by which GoLoco binding motifs inhibit the release of GDP from G?i.

ABSTRACT: GoLoco (GL) motif-containing proteins regulate G protein signaling by binding to G? subunit and acting as guanine nucleotide dissociation inhibitors. GLs of LGN are also known to bind the GDP form of G?(i/o) during asymmetric cell division. Here, we show that the C-terminal GL domain of LGN binds four molecules of G?(i)·GDP. The crystal structures of G?(i)·GDP in complex with LGN GL3 and GL4, respectively, reveal distinct GL/G?(i) interaction features when compared with the only high resolution structure known with GL/G?(i) interaction between RGS14 and G?(i1.) Only a few residues C-terminal to the conserved GL sequence are required for LGN GLs to bind to G?(i)·GDP. A highly conserved "double Arg finger" sequence (R?(D/E)(D/E)QR) is responsible for LGN GL to bind to GDP bound to G?(i). Together with the sequence alignment, we suggest that the LGN GL/G?(i) interaction represents a general binding mode between GL motifs and G?(i). We also show that LGN GLs are potent guanine nucleotide dissociation inhibitors.

SUBMITTER: Jia M

PROVIDER: S-EPMC3481280 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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Crystal structures of the scaffolding protein LGN reveal the general mechanism by which GoLoco binding motifs inhibit the release of GDP from Gαi.

Jia Min M Li Jianchao J Li Jianchao J Zhu Jinwei J Wen Wenyu W Zhang Mingjie M Wang Wenning W

The Journal of biological chemistry 20120905 44

GoLoco (GL) motif-containing proteins regulate G protein signaling by binding to Gα subunit and acting as guanine nucleotide dissociation inhibitors. GLs of LGN are also known to bind the GDP form of Gα(i/o) during asymmetric cell division. Here, we show that the C-terminal GL domain of LGN binds four molecules of Gα(i)·GDP. The crystal structures of Gα(i)·GDP in complex with LGN GL3 and GL4, respectively, reveal distinct GL/Gα(i) interaction features when compared with the only high resolution ...[more]

PMID: 22952234

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Project description:Rhizobial NodZ ?1,6-fucosyltransferase (?1,6-FucT) catalyzes the transfer of the fucose (Fuc) moiety from guanosine 5'-diphosphate-?-L-fucose to the reducing end of the chitin oligosaccharide core during Nod-factor (NF) biosynthesis. NF is a key signalling molecule required for successful symbiosis with a legume host for atmospheric nitrogen fixation. To date, only two ?1,6-FucT structures have been determined, both without any donor or acceptor molecule that could highlight the structural background of the catalytic mechanism. Here, the first crystal structures of ?1,6-FucT in complex with its substrate GDP-Fuc and with GDP, which is a byproduct of the enzymatic reaction, are presented. The crystal of the complex with GDP-Fuc was obtained through soaking of native NodZ crystals with the ligand and its structure has been determined at 2.35?Å resolution. The fucose residue is exposed to solvent and is disordered. The enzyme-product complex crystal was obtained by cocrystallization with GDP and an acceptor molecule, penta-N-acetyl-L-glucosamine (penta-NAG). The structure has been determined at 1.98?Å resolution, showing that only the GDP molecule is present in the complex. In both structures the ligands are located in a cleft formed between the two domains of NodZ and extend towards the C-terminal domain, but their conformations differ significantly. The structures revealed that residues in three regions of the C-terminal domain, which are conserved among ?1,2-, ?1,6- and protein O-fucosyltransferases, are involved in interactions with the sugar-donor molecule. There is also an interaction with the side chain of Tyr45 in the N-terminal domain, which is very unusual for a GT-B-type glycosyltransferase. Only minor conformational changes of the protein backbone are observed upon ligand binding. The only exception is a movement of the loop located between strand ?C2 and helix ?C3. In addition, there is a shift of the ?C3 helix itself upon GDP-Fuc binding.

Dataset Information

Crystal structures of the scaffolding protein LGN reveal the general mechanism by which GoLoco binding motifs inhibit the release of GDP from G?i.

Publications

Crystal structures of the scaffolding protein LGN reveal the general mechanism by which GoLoco binding motifs inhibit the release of GDP from Gαi.

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