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Conservation of the TRAPPII-specific subunits of a Ypt/Rab exchanger complex.

Cox R, Chen SH, Yoo E, Segev N - BMC Evol. Biol. (2007)

Bottom Line: However, we show here that the yeast Trs130 does not function as a trans-membrane protein, and the human TMEM1 does not contain putative TMDs.We suggest that the function of both NIBP and TMEM1 in the regulation of intra-cellular trafficking is conserved from yeast to man.The conserved domains and amino acids discovered here can be used for functional analysis that should help to resolve the differences in the assigned functions of these proteins in fungi and animals.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biological Sciences, Laboratory for Molecular Biology, University of Illinois at Chicago, Chicago, IL 60607, USA. randal@randalcox.net <randal@randalcox.net>

ABSTRACT

Background: Ypt/Rab GTPases and their GEF activators regulate intra-cellular trafficking in all eukaryotic cells. In S. cerivisiae, the modular TRAPP complex acts as a GEF for the Golgi gatekeepers: Ypt1 and the functional pair Ypt31/32. While TRAPPI, which acts in early Golgi, is conserved from fungi to animals, not much is known about TRAPPII, which acts in late Golgi and consists of TRAPPI plus three additional subunits.

Results: Here, we show a phylogenetic analysis of the three TRAPPII-specific subunits. One copy of each of the two essential subunits, Trs120 and Trs130, is present in almost every fully sequenced eukaryotic genome. Moreover, the primary, as well as the predicted secondary, structure of the Trs120- and Trs130-related sequences are conserved from fungi to animals. The mammalian orthologs of Trs120 and Trs130, NIBP and TMEM1, respectively, are candidates for human disorders. Currently, NIBP is implicated in signaling, and TMEM1 is suggested to have trans-membrane domains (TMDs) and to function as a membrane channel. However, we show here that the yeast Trs130 does not function as a trans-membrane protein, and the human TMEM1 does not contain putative TMDs. The non-essential subunit, Trs65, is conserved only among many fungi and some unicellular eukaryotes. Multiple alignment analysis of each TRAPPII-specific subunit revealed conserved domains that include highly conserved amino acids.

Conclusion: We suggest that the function of both NIBP and TMEM1 in the regulation of intra-cellular trafficking is conserved from yeast to man. The conserved domains and amino acids discovered here can be used for functional analysis that should help to resolve the differences in the assigned functions of these proteins in fungi and animals.

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Model for the conserved structure and function of the TRAPPI and TRAPPII complexes. TRAPP complexes mediate exocytic trafficking from the ER, through the Golgi, to the plasma membrane. The TRAPPI complex (left) is shown as a quadrilateral with subunits indicated as triangular sections. Subunits are 3-Bet3, 5-Bet5, 20-Trs20, 23-Trs23, 31-Trs31, 33-Trs33. The Bet3 family (3, 31, 33), are shown as identically light gray triangular sections. The Bet5 family (5,20,23) are shown as identically dark gray triangular sections. The displayed arrangement of components is derived from Kim et al., 2006 [17]. The TRAPPII complex (right) includes all the TRAPPI components plus the three TRAPPII-specific subunits shown in the trapezoidal shape above TRAPPI. In both complexes, subunits essential for viability are labeled in black letters, while non-essential subunits are shown in gray letters. Functionally, TRAPPI is the GEF for Ypt1, the GTPase (GTPases are shown as triangles) that regulates entry into the Golgi, whereas TRAPPII is the GEF for Ypt31/32, the GTPases that regulate exit from the Golgi [16]. All shapes have areas proportional to the corresponding amino acid lengths, except for Trs85, which is larger than shown.
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Figure 7: Model for the conserved structure and function of the TRAPPI and TRAPPII complexes. TRAPP complexes mediate exocytic trafficking from the ER, through the Golgi, to the plasma membrane. The TRAPPI complex (left) is shown as a quadrilateral with subunits indicated as triangular sections. Subunits are 3-Bet3, 5-Bet5, 20-Trs20, 23-Trs23, 31-Trs31, 33-Trs33. The Bet3 family (3, 31, 33), are shown as identically light gray triangular sections. The Bet5 family (5,20,23) are shown as identically dark gray triangular sections. The displayed arrangement of components is derived from Kim et al., 2006 [17]. The TRAPPII complex (right) includes all the TRAPPI components plus the three TRAPPII-specific subunits shown in the trapezoidal shape above TRAPPI. In both complexes, subunits essential for viability are labeled in black letters, while non-essential subunits are shown in gray letters. Functionally, TRAPPI is the GEF for Ypt1, the GTPase (GTPases are shown as triangles) that regulates entry into the Golgi, whereas TRAPPII is the GEF for Ypt31/32, the GTPases that regulate exit from the Golgi [16]. All shapes have areas proportional to the corresponding amino acid lengths, except for Trs85, which is larger than shown.

Mentions: We have previously suggested a role for the TRAPP complex in the coordination of entry into and exit from the Golgi [14,16], and for the TRAPPII-specific subunits, in the specificity switch of the GEF activity of TRAPP from Ypt1 to Ypt 31/32 ([16], and Figure 7). Based on our functional analysis of the S. cerivisiae Trs120 and Trs130, we propose a number of protein-protein interactions for the two essential TRAPPII-specific subunits. We predict at least two protein-protein interactions for Trs120, with Trs130 and with TRAPPI [16]. The four Trs120 conserved domains (I-III, and part of IV), which are essential for S. cerevisiae, are candidates for these interactions. For Trs130, we predict at least two protein-protein interactions and a possible catalytic role in the Ypt31 GEF activity of TRAPPII [16]. The two conserved Trs130 domains that are essential for S. cerevisiae viability, I and II, are candidates for these functions. The identification of Trs120- and Trs130-conserved domains and HC amino acids will allow future functional analysis of the separate domains of these large proteins.


Conservation of the TRAPPII-specific subunits of a Ypt/Rab exchanger complex.

Cox R, Chen SH, Yoo E, Segev N - BMC Evol. Biol. (2007)

Model for the conserved structure and function of the TRAPPI and TRAPPII complexes. TRAPP complexes mediate exocytic trafficking from the ER, through the Golgi, to the plasma membrane. The TRAPPI complex (left) is shown as a quadrilateral with subunits indicated as triangular sections. Subunits are 3-Bet3, 5-Bet5, 20-Trs20, 23-Trs23, 31-Trs31, 33-Trs33. The Bet3 family (3, 31, 33), are shown as identically light gray triangular sections. The Bet5 family (5,20,23) are shown as identically dark gray triangular sections. The displayed arrangement of components is derived from Kim et al., 2006 [17]. The TRAPPII complex (right) includes all the TRAPPI components plus the three TRAPPII-specific subunits shown in the trapezoidal shape above TRAPPI. In both complexes, subunits essential for viability are labeled in black letters, while non-essential subunits are shown in gray letters. Functionally, TRAPPI is the GEF for Ypt1, the GTPase (GTPases are shown as triangles) that regulates entry into the Golgi, whereas TRAPPII is the GEF for Ypt31/32, the GTPases that regulate exit from the Golgi [16]. All shapes have areas proportional to the corresponding amino acid lengths, except for Trs85, which is larger than shown.
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Related In: Results  -  Collection

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Figure 7: Model for the conserved structure and function of the TRAPPI and TRAPPII complexes. TRAPP complexes mediate exocytic trafficking from the ER, through the Golgi, to the plasma membrane. The TRAPPI complex (left) is shown as a quadrilateral with subunits indicated as triangular sections. Subunits are 3-Bet3, 5-Bet5, 20-Trs20, 23-Trs23, 31-Trs31, 33-Trs33. The Bet3 family (3, 31, 33), are shown as identically light gray triangular sections. The Bet5 family (5,20,23) are shown as identically dark gray triangular sections. The displayed arrangement of components is derived from Kim et al., 2006 [17]. The TRAPPII complex (right) includes all the TRAPPI components plus the three TRAPPII-specific subunits shown in the trapezoidal shape above TRAPPI. In both complexes, subunits essential for viability are labeled in black letters, while non-essential subunits are shown in gray letters. Functionally, TRAPPI is the GEF for Ypt1, the GTPase (GTPases are shown as triangles) that regulates entry into the Golgi, whereas TRAPPII is the GEF for Ypt31/32, the GTPases that regulate exit from the Golgi [16]. All shapes have areas proportional to the corresponding amino acid lengths, except for Trs85, which is larger than shown.
Mentions: We have previously suggested a role for the TRAPP complex in the coordination of entry into and exit from the Golgi [14,16], and for the TRAPPII-specific subunits, in the specificity switch of the GEF activity of TRAPP from Ypt1 to Ypt 31/32 ([16], and Figure 7). Based on our functional analysis of the S. cerivisiae Trs120 and Trs130, we propose a number of protein-protein interactions for the two essential TRAPPII-specific subunits. We predict at least two protein-protein interactions for Trs120, with Trs130 and with TRAPPI [16]. The four Trs120 conserved domains (I-III, and part of IV), which are essential for S. cerevisiae, are candidates for these interactions. For Trs130, we predict at least two protein-protein interactions and a possible catalytic role in the Ypt31 GEF activity of TRAPPII [16]. The two conserved Trs130 domains that are essential for S. cerevisiae viability, I and II, are candidates for these functions. The identification of Trs120- and Trs130-conserved domains and HC amino acids will allow future functional analysis of the separate domains of these large proteins.

Bottom Line: However, we show here that the yeast Trs130 does not function as a trans-membrane protein, and the human TMEM1 does not contain putative TMDs.We suggest that the function of both NIBP and TMEM1 in the regulation of intra-cellular trafficking is conserved from yeast to man.The conserved domains and amino acids discovered here can be used for functional analysis that should help to resolve the differences in the assigned functions of these proteins in fungi and animals.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biological Sciences, Laboratory for Molecular Biology, University of Illinois at Chicago, Chicago, IL 60607, USA. randal@randalcox.net <randal@randalcox.net>

ABSTRACT

Background: Ypt/Rab GTPases and their GEF activators regulate intra-cellular trafficking in all eukaryotic cells. In S. cerivisiae, the modular TRAPP complex acts as a GEF for the Golgi gatekeepers: Ypt1 and the functional pair Ypt31/32. While TRAPPI, which acts in early Golgi, is conserved from fungi to animals, not much is known about TRAPPII, which acts in late Golgi and consists of TRAPPI plus three additional subunits.

Results: Here, we show a phylogenetic analysis of the three TRAPPII-specific subunits. One copy of each of the two essential subunits, Trs120 and Trs130, is present in almost every fully sequenced eukaryotic genome. Moreover, the primary, as well as the predicted secondary, structure of the Trs120- and Trs130-related sequences are conserved from fungi to animals. The mammalian orthologs of Trs120 and Trs130, NIBP and TMEM1, respectively, are candidates for human disorders. Currently, NIBP is implicated in signaling, and TMEM1 is suggested to have trans-membrane domains (TMDs) and to function as a membrane channel. However, we show here that the yeast Trs130 does not function as a trans-membrane protein, and the human TMEM1 does not contain putative TMDs. The non-essential subunit, Trs65, is conserved only among many fungi and some unicellular eukaryotes. Multiple alignment analysis of each TRAPPII-specific subunit revealed conserved domains that include highly conserved amino acids.

Conclusion: We suggest that the function of both NIBP and TMEM1 in the regulation of intra-cellular trafficking is conserved from yeast to man. The conserved domains and amino acids discovered here can be used for functional analysis that should help to resolve the differences in the assigned functions of these proteins in fungi and animals.

Show MeSH