5azx
Crystal structure of p24delta1 GOLD domain (native 1)
Structural highlights
FunctionTMEDA_RAT Involved in vesicular protein trafficking. Mainly functions in the early secretory pathway. Thought to act as cargo receptor at the lumenal side for incorporation of secretory cargo molecules into transport vesicles and to be involved in vesicle coat formation at the cytoplasmic side. In COPII vesicle-mediated anterograde transport involved in the transport of GPI-anchored proteins and proposed to act together with TMED2 as their cargo receptor; the function specifically implies SEC24C and SEC24D of the COPII vesicle coat and lipid raft-like microdomains of the ER. Recognizes GPI anchors structural remodeled in the ER by PGAP1 and MPPE1. In COPI vesicle-mediated retrograde transport involved in the biogenesis of COPI vesicles and vesicle coat recruitment. On Golgi membranes, acts as primary receptor for ARF1-GDP which is involved in COPI-vesicle formation. Increases coatomer-dependent GTPase-activating activity of ARFGAP2. Involved in trafficking of G protein-coupled receptors (GPCRs). Regulates F2LR1, OPRM1 and P2RY4 exocytic trafficking from the Golgi to the plasma membrane thus contributing to receptor resensitization. Involved in trafficking of amyloid beta A4 protein and soluble APP-beta release (independent of modulation of gamma-secretase activity). As part of the presenilin-dependent gamma-secretase complex regulates gamma-cleavages of the amyloid beta A4 protein to yield amyloid-beta 40 (Abeta40). Involved in organization of the Golgi apparatus (By similarity). Publication Abstract from PubMedThe p24 family consists of four subfamilies (p24alpha, p24beta, p24gamma, and p24delta), and the proteins are thought to form hetero-oligomeric complexes for efficient transport of cargo proteins from the endoplasmic reticulum to the Golgi apparatus. The proteins possess a conserved luminal Golgi dynamics (GOLD) domain, whose functions are largely unknown. Here, we present structural and biochemical studies of p24beta1 and p24delta1 GOLD domains. Use of GOLD domain-deleted mutants revealed that the GOLD domain of p24delta1 is required for proper p24 hetero-oligomeric complex formation and efficient transport of GPI-anchored proteins. The p24beta1 and p24delta1 GOLD domains share a common beta-sandwich fold with a characteristic intrasheet disulfide bond. The GOLD domain of p24delta1 crystallized as dimers, allowing the analysis of a homophilic interaction site. Surface plasmon resonance and solution NMR analyses revealed that p24beta1 and p24delta1 GOLD domains interact weakly (Kd= ~10-4M). Bi-protein titration provided interaction site maps. We propose that the heterophilic interaction of p24 GOLD domains contributes to the formation of the p24 hetero-oligomeric complex and to efficient cargo transport. 3D Structure and Interaction of p24beta and p24delta Golgi Dynamics Domains: Implication for p24 Complex Formation and Cargo Transport.,Nagae M, Hirata T, Morita-Matsumoto K, Theiler R, Fujita M, Kinoshita T, Yamaguchi Y J Mol Biol. 2016 Aug 25. pii: S0022-2836(16)30342-4. doi:, 10.1016/j.jmb.2016.08.023. PMID:27569046[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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