The crystal structure of a self-activating G protein alpha subunit reveals its distinct mechanism of signal initiation
In animals, heterotrimeric guanine nucleotide-binding protein (G protein) signaling is initiated by G protein-coupled receptors (GPCRs), which activate G protein α subunits; however, the plant Arabidopsis thaliana lacks canonical GPCRs, and its G protein α subunit (AtGPA1) is self-activating. To inv...
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| Veröffentlicht in: | Science signaling 2011-02, Vol.4 (159), p.ra8-ra8 |
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| creator | Jones, Janice C Duffy, Jeffrey W Machius, Mischa Temple, Brenda R S Dohlman, Henrik G Jones, Alan M |
| description | In animals, heterotrimeric guanine nucleotide-binding protein (G protein) signaling is initiated by G protein-coupled receptors (GPCRs), which activate G protein α subunits; however, the plant Arabidopsis thaliana lacks canonical GPCRs, and its G protein α subunit (AtGPA1) is self-activating. To investigate how AtGPA1 becomes activated, we determined its crystal structure. AtGPA1 is structurally similar to animal G protein α subunits, but our crystallographic and biophysical studies revealed that it had distinct properties. Notably, the helical domain of AtGPA1 displayed pronounced intrinsic disorder and a tendency to disengage from the Ras domain of the protein. Domain substitution experiments showed that the helical domain of AtGPA1 was necessary for self-activation and sufficient to confer self-activation to an animal G protein α subunit. These findings reveal the structural basis for a mechanism for G protein activation in Arabidopsis that is distinct from the well-established mechanism found in animals. |
| doi_str_mv | 10.1126/scisignal.2001446 |
| format | Article |
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To investigate how AtGPA1 becomes activated, we determined its crystal structure. AtGPA1 is structurally similar to animal G protein α subunits, but our crystallographic and biophysical studies revealed that it had distinct properties. Notably, the helical domain of AtGPA1 displayed pronounced intrinsic disorder and a tendency to disengage from the Ras domain of the protein. Domain substitution experiments showed that the helical domain of AtGPA1 was necessary for self-activation and sufficient to confer self-activation to an animal G protein α subunit. 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To investigate how AtGPA1 becomes activated, we determined its crystal structure. AtGPA1 is structurally similar to animal G protein α subunits, but our crystallographic and biophysical studies revealed that it had distinct properties. Notably, the helical domain of AtGPA1 displayed pronounced intrinsic disorder and a tendency to disengage from the Ras domain of the protein. Domain substitution experiments showed that the helical domain of AtGPA1 was necessary for self-activation and sufficient to confer self-activation to an animal G protein α subunit. These findings reveal the structural basis for a mechanism for G protein activation in Arabidopsis that is distinct from the well-established mechanism found in animals.</description><subject>Adenosine Diphosphate - chemistry</subject><subject>Adenosine Diphosphate - metabolism</subject><subject>Adenosine Triphosphate - chemistry</subject><subject>Adenosine Triphosphate - metabolism</subject><subject>Amino Acid Sequence</subject><subject>Arabidopsis Proteins - chemistry</subject><subject>Arabidopsis Proteins - genetics</subject><subject>Arabidopsis Proteins - metabolism</subject><subject>Circular Dichroism</subject><subject>Crystallization</subject><subject>GTP-Binding Protein alpha Subunits - chemistry</subject><subject>GTP-Binding Protein alpha Subunits - genetics</subject><subject>GTP-Binding Protein alpha Subunits - metabolism</subject><subject>Guanine Nucleotide Exchange Factors - chemistry</subject><subject>Guanine Nucleotide Exchange Factors - metabolism</subject><subject>Kinetics</subject><subject>Models, Molecular</subject><subject>Molecular Sequence Data</subject><subject>Mutation</subject><subject>Protein Binding</subject><subject>Protein Folding</subject><subject>Protein Structure, Secondary</subject><subject>Protein Structure, Tertiary</subject><subject>Receptors, G-Protein-Coupled - chemistry</subject><subject>Receptors, G-Protein-Coupled - metabolism</subject><subject>Sequence Homology, Amino Acid</subject><subject>Signal Transduction</subject><subject>X-Ray Diffraction</subject><issn>1945-0877</issn><issn>1937-9145</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkctKxDAUhoMo3h_AjWTnqpqkuXUjiHgDwY2uQyY9nYm06ZikA769GWYcdJXA-f4vJ_wIXVByTSmTN8n55OfB9teMEMq53EPHtKlV1VAu9td3LiqilTpCJyl9EiIpY80hOmK0JpyK5hit3heAXfxO2fY45Ti5PEXAY4ctTtB3lXXZr2z2YY6f8DKOGXzAtl8uynyaTcFnHGEFtk_Y54RbnwrrMh7ALWzwaVi7NltiX2hfXGM4QwddicD59jxFH48P7_fP1evb08v93Wvl6kbnyioGsqYzCTVoq1zLZ9JZRQXnoCSXmpOu7WTDlbaNll2rFeXSMSG1K79V9Sm63XiX02yA1kHI0fZmGf1g47cZrTf_J8EvzHxcmVoIytRacLUVxPFrgpTN4JODvrcBxikZXTCmpBCFpBvSxTGlCN3uFUrMui6zq8ts6yqZy7_r7RK__dQ_NOyWeA</recordid><startdate>20110208</startdate><enddate>20110208</enddate><creator>Jones, Janice C</creator><creator>Duffy, Jeffrey W</creator><creator>Machius, Mischa</creator><creator>Temple, Brenda R S</creator><creator>Dohlman, Henrik G</creator><creator>Jones, Alan M</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20110208</creationdate><title>The crystal structure of a self-activating G protein alpha subunit reveals its distinct mechanism of signal initiation</title><author>Jones, Janice C ; Duffy, Jeffrey W ; Machius, Mischa ; Temple, Brenda R S ; Dohlman, Henrik G ; Jones, Alan M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c398t-a72e631b6e3e8a7cd4b6ca71544e7646840fdf69478a986fd87146c2568c00673</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adenosine Diphosphate - chemistry</topic><topic>Adenosine Diphosphate - metabolism</topic><topic>Adenosine Triphosphate - chemistry</topic><topic>Adenosine Triphosphate - metabolism</topic><topic>Amino Acid Sequence</topic><topic>Arabidopsis Proteins - chemistry</topic><topic>Arabidopsis Proteins - genetics</topic><topic>Arabidopsis Proteins - metabolism</topic><topic>Circular Dichroism</topic><topic>Crystallization</topic><topic>GTP-Binding Protein alpha Subunits - chemistry</topic><topic>GTP-Binding Protein alpha Subunits - genetics</topic><topic>GTP-Binding Protein alpha Subunits - metabolism</topic><topic>Guanine Nucleotide Exchange Factors - chemistry</topic><topic>Guanine Nucleotide Exchange Factors - metabolism</topic><topic>Kinetics</topic><topic>Models, Molecular</topic><topic>Molecular Sequence Data</topic><topic>Mutation</topic><topic>Protein Binding</topic><topic>Protein Folding</topic><topic>Protein Structure, Secondary</topic><topic>Protein Structure, Tertiary</topic><topic>Receptors, G-Protein-Coupled - chemistry</topic><topic>Receptors, G-Protein-Coupled - metabolism</topic><topic>Sequence Homology, Amino Acid</topic><topic>Signal Transduction</topic><topic>X-Ray Diffraction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jones, Janice C</creatorcontrib><creatorcontrib>Duffy, Jeffrey W</creatorcontrib><creatorcontrib>Machius, Mischa</creatorcontrib><creatorcontrib>Temple, Brenda R S</creatorcontrib><creatorcontrib>Dohlman, Henrik G</creatorcontrib><creatorcontrib>Jones, Alan M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Science signaling</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jones, Janice C</au><au>Duffy, Jeffrey W</au><au>Machius, Mischa</au><au>Temple, Brenda R S</au><au>Dohlman, Henrik G</au><au>Jones, Alan M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The crystal structure of a self-activating G protein alpha subunit reveals its distinct mechanism of signal initiation</atitle><jtitle>Science signaling</jtitle><addtitle>Sci Signal</addtitle><date>2011-02-08</date><risdate>2011</risdate><volume>4</volume><issue>159</issue><spage>ra8</spage><epage>ra8</epage><pages>ra8-ra8</pages><issn>1945-0877</issn><eissn>1937-9145</eissn><abstract>In animals, heterotrimeric guanine nucleotide-binding protein (G protein) signaling is initiated by G protein-coupled receptors (GPCRs), which activate G protein α subunits; however, the plant Arabidopsis thaliana lacks canonical GPCRs, and its G protein α subunit (AtGPA1) is self-activating. To investigate how AtGPA1 becomes activated, we determined its crystal structure. AtGPA1 is structurally similar to animal G protein α subunits, but our crystallographic and biophysical studies revealed that it had distinct properties. Notably, the helical domain of AtGPA1 displayed pronounced intrinsic disorder and a tendency to disengage from the Ras domain of the protein. Domain substitution experiments showed that the helical domain of AtGPA1 was necessary for self-activation and sufficient to confer self-activation to an animal G protein α subunit. These findings reveal the structural basis for a mechanism for G protein activation in Arabidopsis that is distinct from the well-established mechanism found in animals.</abstract><cop>United States</cop><pmid>21304159</pmid><doi>10.1126/scisignal.2001446</doi><oa>free_for_read</oa></addata></record> |
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| source | American Association for the Advancement of Science; MEDLINE |
| subjects | Adenosine Diphosphate - chemistry Adenosine Diphosphate - metabolism Adenosine Triphosphate - chemistry Adenosine Triphosphate - metabolism Amino Acid Sequence Arabidopsis Proteins - chemistry Arabidopsis Proteins - genetics Arabidopsis Proteins - metabolism Circular Dichroism Crystallization GTP-Binding Protein alpha Subunits - chemistry GTP-Binding Protein alpha Subunits - genetics GTP-Binding Protein alpha Subunits - metabolism Guanine Nucleotide Exchange Factors - chemistry Guanine Nucleotide Exchange Factors - metabolism Kinetics Models, Molecular Molecular Sequence Data Mutation Protein Binding Protein Folding Protein Structure, Secondary Protein Structure, Tertiary Receptors, G-Protein-Coupled - chemistry Receptors, G-Protein-Coupled - metabolism Sequence Homology, Amino Acid Signal Transduction X-Ray Diffraction |
| title | The crystal structure of a self-activating G protein alpha subunit reveals its distinct mechanism of signal initiation |
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