Structure, exchange determinants, and family-wide rab specificity of the tandem helical bundle and Vps9 domains of Rabex-5
| dc.contributor.author | Delprato, Anna M. | |
| dc.contributor.author | Merithew, Eric Lee | |
| dc.contributor.author | Lambright, David G. | |
| dc.date | 2022-08-11T08:08:57.000 | |
| dc.date.accessioned | 2022-08-23T16:13:20Z | |
| dc.date.available | 2022-08-23T16:13:20Z | |
| dc.date.issued | 2004-09-02 | |
| dc.date.submitted | 2008-08-29 | |
| dc.identifier.citation | Cell. 2004 Sep 3;118(5):607-17. <a href="http://dx.doi.org/10.1016/j.cell.2004.08.009">Link to article on publisher's site</a> | |
| dc.identifier.issn | 0092-8674 (Print) | |
| dc.identifier.doi | 10.1016/j.cell.2004.08.009 | |
| dc.identifier.pmid | 15339665 | |
| dc.identifier.uri | http://hdl.handle.net/20.500.14038/33597 | |
| dc.description.abstract | The Rab5 GTPase, an essential regulator of endocytosis and endosome biogenesis, is activated by guanine-nucleotide exchange factors (GEFs) that contain a Vps9 domain. Here, we show that the catalytic core of the Rab GEF Rabex-5 has a tandem architecture consisting of a Vps9 domain stabilized by an indispensable helical bundle. A family-wide analysis of Rab specificity demonstrates high selectivity for Rab5 subfamily GTPases. Conserved exchange determinants map to a common surface of the Vps9 domain, which recognizes invariant aromatic residues in the switch regions of Rab GTPases and selects for the Rab5 subfamily by requiring a small nonacidic residue preceding a critical phenylalanine in the switch I region. These and other observations reveal unexpected similarity with the Arf exchange site in the Sec7 domain. | |
| dc.language.iso | en_US | |
| dc.relation | <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15339665&dopt=Abstract ">Link to article in PubMed</a> | |
| dc.relation.url | http://dx.doi.org/10.1016/j.cell.2004.08.009 | |
| dc.subject | Amino Acid Sequence; Animals; Carrier Proteins; Catalytic Domain; Endocytosis; Guanine Nucleotide Exchange Factors; Humans; *Intracellular Signaling Peptides and Proteins; Models, Molecular; Molecular Sequence Data; Mutation; Phenylalanine; Protein Binding; Protein Structure, Secondary; Sequence Homology, Amino Acid; rab GTP-Binding Proteins; rab5 GTP-Binding Proteins | |
| dc.subject | Life Sciences | |
| dc.subject | Medicine and Health Sciences | |
| dc.title | Structure, exchange determinants, and family-wide rab specificity of the tandem helical bundle and Vps9 domains of Rabex-5 | |
| dc.type | Journal Article | |
| dc.source.journaltitle | Cell | |
| dc.source.volume | 118 | |
| dc.source.issue | 5 | |
| dc.identifier.legacycoverpage | https://escholarship.umassmed.edu/gsbs_sp/267 | |
| dc.identifier.contextkey | 610010 | |
| html.description.abstract | <p>The Rab5 GTPase, an essential regulator of endocytosis and endosome biogenesis, is activated by guanine-nucleotide exchange factors (GEFs) that contain a Vps9 domain. Here, we show that the catalytic core of the Rab GEF Rabex-5 has a tandem architecture consisting of a Vps9 domain stabilized by an indispensable helical bundle. A family-wide analysis of Rab specificity demonstrates high selectivity for Rab5 subfamily GTPases. Conserved exchange determinants map to a common surface of the Vps9 domain, which recognizes invariant aromatic residues in the switch regions of Rab GTPases and selects for the Rab5 subfamily by requiring a small nonacidic residue preceding a critical phenylalanine in the switch I region. These and other observations reveal unexpected similarity with the Arf exchange site in the Sec7 domain.</p> | |
| dc.identifier.submissionpath | gsbs_sp/267 | |
| dc.contributor.department | Program in Molecular Medicine and Department of Biochemistry and Molecular Pharmacology | |
| dc.contributor.department | Graduate School of Biomedical Sciences | |
| dc.source.pages | 607-17 |
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