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: 10.47). 02/2002; 3(5):research0023. DOI: 10.1186/gb-2002-3-5-research0023
Source: PubMed

ABSTRACT 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.

Download full-text


Available from: Vivek Anantharaman, Jul 27, 2015
  • Source
    • "Indeed it has been proposed that oligomerization is required for the proper localization of p24 proteins (Emery et al., 2000; Ciufo and Boyd, 2000). The luminal GOLD domain, present in several proteins involved in Golgi dynamics, 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). "
    [Show abstract] [Hide abstract]
    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. It has previously been shown that transiently expressed red fluorescent protein (RFP)-p24δ5 localizes to the endoplasmic reticulum (ER) as a consequence of highly efficient COPI-based recycling from the Golgi apparatus. Using specific antibodies, endogenous p24δ5 has now been localized to the ER and p24β2 to the Golgi apparatus in Arabidopsis root tip cells by immunogold electron microscopy. The relative contributions of the cytosolic tail and the luminal domains to p24δ5 trafficking have also been characterized. It is demonstrated that whereas the dilysine motif in the cytoplasmic tail determines the location of p24δ5 in the early secretory pathway, the luminal domain may contribute to its distribution downstream of the Golgi apparatus. By using knock-out mutants and co-immunoprecipitation experiments, it is shown that p24δ5 and p24β2 interact with each other. Finally, it is shown that p24δ5 and p24β2 exhibit coupled trafficking at the ER-Golgi interface. It is proposed that p24δ5 and p24β2 interact with each other at ER export sites for ER exit and coupled transport to the Golgi apparatus. Once in the Golgi, p24δ5 interacts very efficiently with the COPI machinery for retrograde transport back to the ER.
    Journal of Experimental Botany 05/2012; 63(11):4243-61. DOI:10.1093/jxb/ers112 · 5.79 Impact Factor
  • Source
    • "The GOLD domain is typically 90–150 aa long and folds into six or seven b-strands. This domain has been identified in several proteins with roles in Golgi dynamics and secretion including p24 proteins and Sec14 proteins, and is thought to serve as a common denominator in protein–protein interactions (Anantharaman and Aravind, 2002). It would be interesting to investigate whether the AiV proteins have the ability to bind to other GOLD domain-containing proteins. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Phosphatidylinositol 4-kinase IIIβ (PI4KB) is a host factor required for genome RNA replication of enteroviruses, small non-enveloped viruses belonging to the family Picornaviridae. Here, we demonstrated that PI4KB is also essential for genome replication of another picornavirus, Aichi virus (AiV), but is recruited to the genome replication sites by a different strategy from that utilized by enteroviruses. AiV non-structural proteins, 2B, 2BC, 2C, 3A, and 3AB, interacted with a Golgi protein, acyl-coenzyme A binding domain containing 3 (ACBD3). Furthermore, we identified previously unknown interaction between ACBD3 and PI4KB, which provides a novel manner of Golgi recruitment of PI4KB. Knockdown of ACBD3 or PI4KB suppressed AiV RNA replication. The viral proteins, ACBD3, PI4KB, and phophatidylinositol-4-phosphate (PI4P) localized to the viral RNA replication sites. AiV replication and recruitment of PI4KB to the RNA replication sites were not affected by brefeldin A, in contrast to those in enterovirus infection. These results indicate that a viral protein/ACBD3/PI4KB complex is formed to synthesize PI4P at the AiV RNA replication sites and plays an essential role in viral RNA replication.
    The EMBO Journal 11/2011; 31(3):754-66. DOI:10.1038/emboj.2011.429 · 10.75 Impact Factor
  • Source
    • "CRAL/TRIO domains form hydrophobic binding pockets that bind small hydrophobic ligands (Bateman et al., 2000; Sha et al., 1998; Stocker et al., 2002; Stocker and Baumann, 2003; Panagabko et al., 2003). GOLD (Golgi dynamics) domains were identified by protein alignments and are of unknown function (Stocker et al., 2002; Anantharaman and Aravind, 2002). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The activation of the protein kinase Raf at the cell membrane is a critical step in cell signaling during development, but the mechanisms that regulate Raf activity remain incompletely defined. We previously demonstrated that the C. elegans cgr-1 gene encodes a CRAL/TRIO domain-containing protein that is a critical modulator of Ras-dependent cell fate specification during C. elegans development. Here we identify the mammalian alpha-tocopherol associated protein-1 (TAP-1) as a functional ortholog of cgr-1. TAP-1 mRNA was expressed in many tissues, and TAP-1 protein colocalized with Ras and Raf at the cell membrane. Reducing TAP-1 expression by RNA interference increased Ras/ERK signaling in multiple cell types. These functional studies demonstrate that CRAL/TRIO domain proteins play a conserved role in regulating Ras signaling. Biochemical analyses indicated that TAP-1 operates at the level of Raf, since TAP-1 function negatively regulated the amount of Raf-1 recruited to GTP-bound Ras at the cell membrane. TAP-1 plays a significant physiological role in controlling cell division, since reducing TAP-1 expression increased the oncogenic capacity of Ras transformed human cancer cell lines. These studies identify TAP-1 as a critical modulator of Ras-mediated cellular signaling.
    Developmental Biology 03/2010; 341(2):464-71. DOI:10.1016/j.ydbio.2010.03.003 · 3.64 Impact Factor
Show more