A gold revision of the Golgi Dynamics (GOLD) domain structure and associated cell functionalities

Abstract

The classical secretory pathway is the key membrane-based delivery system in eukaryotic cells. Several families of proteins involved in the secretory pathway, with functionalities going from cargo sorting receptors to the maintenance and dynamics of secretory organelles, share soluble globular domains predicted to mediate protein-protein interactions. One of them is the 'Golgi Dynamics' (GOLD) domain, named after its strong association with the Golgi apparatus. There are many GOLD-containing protein families, such as the transmembrane emp24 domain-containing proteins (TMED/p24 family), animal SEC14-like proteins, human Golgi resident protein ACBD3, a splice variant of TICAM2 called TRAM with GOLD domain, and FYCO1. Here, we critically review the state-of-the-art knowledge of the structures and functions of the main representatives of GOLD-containing proteins in vertebrates. We provide the first unified description of the GOLD domain structure across different families since the first high-resolution structure was determined. With a brand-new update on the definition of the GOLD domain, we also discuss how its tertiary structure fits the b-sandwich-like fold map and give exciting new directions for forthcoming studies.

Structural insights into ion conduction by novel cation channel, TMEM87A, in Golgi apparatus

“…To investigate the structural basis of the TMEM87A ELD and TMD for its physiological roles we initially searched for structural homology of the hTMEM87A ELD using the Dali server 20 . We found that the β-sandwich domain of the hTMEM87A ELD resembles a ‘Golgi Dynamics’ (GOLD) domain present in p24 family proteins and SEC14-like protein 3 (PDB: 5AZW 21 , 5GU5 22 and 4UYB, Fig.3a and Extended Data Fig.6a ), which are implicated in the secretory pathway such as cargo sorting and membrane trafficking 23,24 . Interestingly, the sequence identity of the ELD across hTMEM87 family members is relatively low compared to that of the TMD (Sequence identity for ELD and TMD between hTMEM87A and hTMEM87B: 24.7 % and 63.1 %, respectively).…”

“…3a and Extended Data Fig. 6a), which are implicated in the secretory pathway such as cargo sorting and membrane trafficking 23,24 . Interestingly, the sequence identity of the ELD across hTMEM87 family members is relatively low compared to that of the TMD (Sequence identity for ELD and TMD between hTMEM87A and hTMEM87B: 24.7 % and 63.1 %, respectively).…”

Structure of the GOLD-domain seven-transmembrane helix protein family member TMEM87A

“…Superposition of the TMEM87A extracellular domain and p24 shows conservation of β strand topology throughout the domain, with differences predominantly in regions connecting β strands including the helix-turn-helix motif in the TMEM87A GOLD domain ( Holm, 2020 ; Nagae et al, 2016 ; Figure 3—figure supplement 1a–c ). GOLD domain proteins have established roles in the secretory pathway ( Nagae et al, 2016 ; Anantharaman and Aravind, 2002 ) and p24 proteins are implicated as cargo receptors for protein transport, with the GOLD domain mediating cargo recognition ( Pastor-Cantizano et al, 2016 ; Mendes and Costa-Filho, 2022 ). Among different p24 proteins, the GOLD domain loops are among the most variable regions and have been hypothesized to recognize different cargo ( Nagae et al, 2016 ).…”

Structure of the GOLD-domain seven-transmembrane helix protein family member TMEM87A

“…5a-c). GOLD domain proteins have established roles in the secretory pathway 27,28 and p24 proteins are implicated as cargo receptors for protein transport, with the GOLD domain mediating cargo recognition 29,30 . Among different p24 proteins, the GOLD domain loops are among the most variable regions and have been hypothesized to recognize different cargo 27 .…”