Structure and mutagenesis of the Dbl homology domain Journal Article
| Authors: | Aghazadeh, B.; Zhu, K.; Kubiseski, T. J.; Liu, G. A.; Pawson, T.; Zheng, Y.; Rosen, M. K. |
| Article Title: | Structure and mutagenesis of the Dbl homology domain |
| Abstract: | Guanine nucleotide exchange factors in the Dbl family activate Rho GTPases by accelerating dissociation of bound GDP, promoting acquisition of the GTP-bound state. Dbl proteins possess a ~200 residue catalytic Dbl- homology (DH) domain, that is arranged in tandem with a C-terminal pleckstrin homology (PH) domain in nearly all cases. Here we report the solution structure of the DH domain of human PAK-interacting exchange protein (βPIX). The domain is composed of 11 α-helices that form a flattened, elongated bundle. The structure explains a large body of mutagenesis data, which, along with sequence comparisons, identify the GTPase interaction site as a surface formed by three conserved helices near the center of one face of the domain. Proximity of the site to the DH C-terminus suggests a means by which PH- ligand interactions may be coupled to DH-GTPase interactions to regulate signaling through the Dbl proteins in vivo. |
| Keywords: | signal transduction; protein expression; frameshift mutation; proto-oncogene proteins; review; protein domain; proteins; blood proteins; cell cycle proteins; nerve tissue proteins; gtp-binding proteins; enzyme activation; amino acid sequence; molecular sequence data; sequence homology, amino acid; sequence alignment; escherichia coli; magnetic resonance spectroscopy; phosphoproteins; models, molecular; mutagenesis, site-directed; protein structure; sequence homology; protein family; site directed mutagenesis; catalytic domain; stereochemistry; gtp phosphohydrolases; guanine nucleotide exchange factors; rho factor; guanosine diphosphate; guanine nucleotide exchange factor; guanosine triphosphatase; caenorhabditis elegans proteins; cdc42 gtp-binding protein; rhoa gtp-binding protein; helminth proteins; pleckstrin; humans; priority journal |
| Journal Title: | Nature Structural Biology |
| Volume: | 5 |
| Issue: | 12 |
| ISSN: | 1072-8368 |
| Publisher: | Nature Publishing Group |
| Date Published: | 1998-12-01 |
| Start Page: | 1098 |
| End Page: | 1107 |
| Language: | English |
| DOI: | 10.1038/4209 |
| PUBMED: | 9846881 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Review -- Export Date: 12 December 2016 -- Source: Scopus |
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