Rab GEFs emerge from their DENN
نویسندگان
چکیده
منابع مشابه
Rab GEFs and GAPs.
Rabs are GTP-binding proteins with conserved functions in membrane trafficking. They are regulated by a diverse group of structurally unrelated GDP-GTP exchange factors (GEFs), and a family of GTP-hydrolysis activating proteins (GAPs) containing the conserved TBC domain. Recent structural and cell biological studies shed new light on the mechanisms of Rab GEF and GAP action, and the cellular tr...
متن کاملThe product of C9orf72, a gene strongly implicated in neurodegeneration, is structurally related to DENN Rab-GEFs
MOTIVATION Fronto-temporal dementia (FTD) and amyotrophic lateral sclerosis (ALS, also called motor neuron disease, MND) are severe neurodegenerative diseases that show considerable overlap at the clinical and cellular level. The most common single mutation in families with FTD or ALS has recently been mapped to a non-coding repeat expansion in the uncharacterized gene C9ORF72. Although a plaus...
متن کاملFamily-wide characterization of the DENN domain Rab GDP-GTP exchange factors
A key requirement for Rab function in membrane trafficking is site-specific activation by GDP-GTP exchange factors (GEFs), but the majority of the 63 human Rabs have no known GEF. We have performed a systematic characterization of the 17 human DENN domain proteins and demonstrated that they are specific GEFs for 10 Rabs. DENND1A/1B localize to clathrin patches at the plasma membrane and activat...
متن کاملInsights regarding guanine nucleotide exchange from the structure of a DENN-domain protein complexed with its Rab GTPase substrate.
Rab GTPases are key regulators of membrane traffic pathways within eukaryotic cells. They are specifically activated by guanine nucleotide exchange factors (GEFs), which convert them from their "inactive" GDP-bound form to the "active" GTP-bound form. In higher eukaryotes, proteins containing DENN-domains comprise a major GEF family. Here we describe at 2.1-Å resolution the first structure of a...
متن کاملDiscovery of Novel DENN Proteins: Implications for the Evolution of Eukaryotic Intracellular Membrane Structures and Human Disease
The tripartite DENN module, comprised of a N-terminal longin domain, followed by DENN, and d-DENN domains, is a GDP-GTP exchange factor (GEFs) for Rab GTPases, which are regulators of practically all membrane trafficking events in eukaryotes. Using sequence and structure analysis we identify multiple novel homologs of the DENN module, many of which can be traced back to the ancestral eukaryote....
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ژورنال
عنوان ژورنال: Journal of Cell Biology
سال: 2010
ISSN: 1540-8140,0021-9525
DOI: 10.1083/jcb.1912iti2