The GOLD domain, a novel protein module involved in Golgi function and secretion

National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.
Genome biology (Impact Factor: 10.81). 02/2002; 3(5):research0023. DOI: 10.1186/gb-2002-3-5-research0023
Source: PubMed


Members of the p24 (p24/gp25L/emp24/Erp) family of proteins have been shown to be critical components of the coated vesicles that are involved in the transportation of cargo molecules from the endoplasmic reticulum to the Golgi complex. The p24 proteins form hetero-oligomeric complexes and are believed to function as receptors for specific secretory cargo.
Using sensitive sequence-profile analysis methods, we identified a novel beta-strand-rich domain, the GOLD (Golgi dynamics) domain, in the p24 proteins and several other proteins with roles in Golgi dynamics and secretion. This domain is predicted to mediate diverse protein-protein interactions. Other than in the p24 proteins, the GOLD domain is always found combined with lipid- or membrane-association domains such as the pleckstrin homology (PH), Sec14p and FYVE domains.
The identification of the GOLD domain could aid in directed investigation of the role of the p24 proteins in the secretion process. The newly detected group of GOLD-domain proteins, which might simultaneously bind membranes and other proteins, point to the existence of a novel class of adaptors that could have a role in the assembly of membrane-associated complexes or in regulating assembly of cargo into membranous vesicles.

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Available from: Vivek Anantharaman, Jul 27, 2015
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    • "The cytoplasmic tail contains binding motifs for the vesicle coat complexes COPI and COPII [11]. At the luminal side, p24 proteins have an N-terminal Golgi dynamics (GOLD) domain, which may play a role in the incorporation of cargo into transport vesicles [9, 12]. The N-terminal luminal domain contains two conserved cysteine residues [13], presumably forming a disulfide bond within the GOLD domain [9]. "
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    ABSTRACT: Rabbit serum produced after transplantation of isolated rat chondrocytes [sensitized rabbit serum (SRS)] demonstrated M r ~ 74- and ~23-kDa (western blot analysis) antigens in rat chondrocyte extracts. Only the latter remained after reduction in 2-mercaptoethanol. Protein sequence analysis of 23-kDa chondrocyte-associated antigen (CAA) revealed that it corresponds to transmembrane Tmp21 protein belonging to the p24 protein family. These proteins mainly participate in the traffic between the endoplasmic reticulum and Golgi complex and in some cells appear also in the membrane of secretory granules and plasmalemma. Tmp21 extracted from chondrocytes was sialylated and ceased to bind SRS after deglycosylation. A previous study from our laboratory indicated that expression of CAA, now identified as sialylated Tmp21, decreased in cultured chondrocytes concomitantly with the decline of collagen type II and aggrecan and the rise of collagen type I and versican expression. Since the sialylated form of Tmp21 (also known as emp24) was not described in other tissues and seems to be specific for chondrocytes, we assume that CAA may be considered a chondrocyte differentiation antigen.
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    • "All p24 proteins consist of a large luminal portion, which includes the GOLD (GOLgi Dynamics) and coiled-coil domains, a single transmembrane domain, and a short cytoplasmic C-terminus which contains motifs for COPI and COPII binding (Supplementary Fig. S1 available at JXB online). Whereas the transmembrane domain seems to recognize a single sphingolipid species (Contreras et al., 2012), the luminal GOLD domain is predicted to be involved in specific protein–protein interactions and has been postulated to interact with putative cargo proteins (Anantharaman and Aravind, 2002; Carney and Bowen, 2004). The coiled-coil domain of p24 proteins enables intermolecular interactions between copies of the same protein, but also between different p24 proteins. "
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    ABSTRACT: p24 proteins are a family of type I membrane proteins localized to compartments of the early secretory pathway and to coat protein I (COPI)- and COPII-coated vesicles. They can be classified, by sequence homology, into four subfamilies, named p24α, p24β, p24γ, and p24δ. In contrast to animals and fungi, plants contain only members of the p24β and p24δ subfamilies, the latter probably including two different subclasses. It has previously been shown that transiently expressed red fluorescent protein (RFP)-p24δ5 (p24δ1 subclass) localizes to the endoplasmic reticulum (ER) at steady state as a consequence of highly efficient COPI-based recycling from the Golgi apparatus. It is now shown that transiently expressed RFP-p24δ9 (p24δ2 subclass) also localizes to the ER. In contrast, transiently expressed green fluorescent protein (GFP)-p24β3 mainly localizes to the Golgi apparatus (as p24β2) and exits the ER in a COPII-dependent manner. Immunogold electron microscopy in Arabidopsis root tip cells using specific antibodies shows that endogenous p24δ9 localizes mainly to the ER but also partially to the cis-Golgi. In contrast, endogenous p24β3 mainly localizes to the Golgi apparatus. By a combination of experiments using transient expression, knock-out mutants, and co-immunoprecipitation, it is proposed that Arabidopsis p24 proteins form different heteromeric complexes (including members of the β and δ subfamilies) which are important for their stability and their coupled trafficking at the ER-Golgi interface. Evidence is also provided for a role for p24δ5 in retrograde Golgi-ER transport of the KDEL-receptor ERD2.
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    • "While it is likely that the complex is a tetramer or larger, the exact composition of the complex and how these components interact with each other in the complex are currently unclear. All p24 proteins have a similar domain organization consisting of an N-terminal signal sequence, a luminal domain termed the GOLD domain (for GOLgi Dynamics)[32], a helical region with a central coiled-coil domain, a transmembrane domain and a short cytoplasmic domain[26](Figs. 1B, 2B). "
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