| GGA autoinhibition revisited. | |
| | |
MedLine Citation:
|
PMID: 20015111 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
The cytosolic adaptors GGA1-3 mediate sorting of transmembrane proteins displaying a C-terminal acidic dileucine motif (DXXLL) in their cytosolic domain. GGA1 and GGA3 contain similar but intrinsic motifs that are believed to serve as autoinhibitory sites activated by the phosphorylation of a serine positioned three residues upstream of the DXXLL motif. In the present study, we have subjected the widely acknowledged concept of GGA1 autoinhibition to a thorough structural and functional examination. We find that (i) the intrinsic motif of GGA1 is inactive, (ii) only C-terminal DXXLL motifs constitute active GGA binding sites, (iii) while aspartates and phosphorylated serines one or two positions upstream of the DXXLL motif increase GGA1 binding, phosphoserines further upstream have little or no influence and (iv) phosphorylation of GGA1 does not affect its conformation or binding to Sortilin and SorLA. Taken together, our findings seem to refute the functional significance of GGA autoinhibition in particular and of intrinsic GGA binding motifs in general. |
| | |
Authors:
|
Jacob F Cramer; Camilla Gustafsen; Manja A Behrens; Cristiano L P Oliveira; Jan Skov Pedersen; Peder Madsen; Claus Munck Petersen; S?ren S Thirup |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-11-10 |
Journal Detail:
|
Title: Traffic (Copenhagen, Denmark) Volume: 11 ISSN: 1600-0854 ISO Abbreviation: Traffic Publication Date: 2010 Feb |
Date Detail:
|
Created Date: 2010-01-18 Completed Date: 2010-04-09 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 100939340 Medline TA: Traffic Country: Denmark |
Other Details:
|
Languages: eng Pagination: 259-73 Citation Subset: IM |
Affiliation:
|
MIND Centre, Department of Molecular Biology, Aarhus University, Gustav Wieds Vej 10 C, DK-8000 Aarhus C, Denmark. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adaptor Proteins, Vesicular Transport
/
antagonists & inhibitors*,
chemistry,
genetics,
metabolism* Amino Acid Motifs Amino Acid Sequence Cell Line Crystallography, X-Ray Humans LDL-Receptor Related Proteins / metabolism Membrane Transport Proteins / metabolism Models, Molecular Molecular Sequence Data Mutation / genetics Phosphoserine Protein Binding Protein Interaction Domains and Motifs Protein Sorting Signals Saccharomyces cerevisiae / genetics Two-Hybrid System Techniques |
| Chemical | |
Reg. No./Substance:
|
0/Adaptor Proteins, Vesicular Transport; 0/GGA adaptor proteins; 0/LDL-Receptor Related Proteins; 0/Membrane Transport Proteins; 0/Protein Sorting Signals; 0/SORL1 protein, human; 0/sortilin; 17885-08-4/Phosphoserine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Cutaneous infiltrates and peripheral blood immune responses in dogs with immunomodulatory-responsive...
Next Document: Thiazolidinediones Induce Rab7-RILP-MAPK-Dependent Juxtanuclear Lysosome Aggregation and Reduce Tumo...