scholarly journals Sequence Features of Mitochondrial Transporter Protein Families

2020 ◽  
Author(s):  
Gergely Gyimesi ◽  
Matthias A. Hediger
Keyword(s):  
Structure Prediction ◽  
Secondary Structure Prediction ◽  
Current Knowledge ◽  
Special Focus ◽  
Protein Sequence Analysis ◽  
Protein Families ◽  
Inner Mitochondrial Membrane ◽  
Mitochondrial Carriers ◽  
Sequence Features ◽  
Mitochondrial Transporter

Mitochondrial carriers facilitate the transfer of small molecules across the inner mitochondrial membrane (IMM) to support mitochondrial function and core cellular processes. In addition to the classical mitochondrial carrier family SLC25, the past decade led to the discovery of additional protein families that exhibit IMM localization and transporter-like properties. These include mitochondrial pyruvate carriers, sideroflexins and mitochondrial cation/H+ exchangers that have been linked to vital physiological functions and disease. Their structures and transport mechanisms are still largely unknown and understudied. Protein sequence analysis per se can often pinpoint hotspots that are of functional or structural importance. In this review, we summarize current knowledge about sequence features of mitochondrial transporters with a special focus on the newly included SLC54, SLC55 and SLC56 families of the SLC solute carrier superfamily. Taking a step further, we combined sequence conservation analysis with transmembrane segment and secondary structure prediction methods to extract residue positions and sequence motifs that likely play a role in substrate binding, binding site gating or structural stability. We hope that our review will help guide future experimental efforts by the scientific community to unravel the transport mechanism and structure of these novel mitochondrial carriers.

scholarly journals Sequence Features of Mitochondrial Transporter Protein Families

Biomolecules ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1611
Author(s):  
Gergely Gyimesi ◽  
Matthias A. Hediger
Keyword(s):  
Secondary Structure Prediction ◽  
Current Knowledge ◽  
Special Focus ◽  
Transport Mechanisms ◽  
Protein Sequence Analysis ◽  
Protein Families ◽  
Mitochondrial Carriers ◽  
Sequence Features ◽  
Mitochondrial Transporter ◽  
Solute Carrier

Mitochondrial carriers facilitate the transfer of small molecules across the inner mitochondrial membrane (IMM) to support mitochondrial function and core cellular processes. In addition to the classical SLC25 (solute carrier family 25) mitochondrial carriers, the past decade has led to the discovery of additional protein families with numerous members that exhibit IMM localization and transporter-like properties. These include mitochondrial pyruvate carriers, sideroflexins, and mitochondrial cation/H+ exchangers. These transport proteins were linked to vital physiological functions and disease. Their structures and transport mechanisms are, however, still largely unknown and understudied. Protein sequence analysis per se can often pinpoint hotspots that are of functional or structural importance. In this review, we summarize current knowledge about the sequence features of mitochondrial transporters with a special focus on the newly included SLC54, SLC55 and SLC56 families of the SLC solute carrier superfamily. Taking a step further, we combine sequence conservation analysis with transmembrane segment and secondary structure prediction methods to extract residue positions and sequence motifs that likely play a role in substrate binding, binding site gating or structural stability. We hope that our review will help guide future experimental efforts by the scientific community to unravel the transport mechanisms and structures of these novel mitochondrial carriers.

scholarly journals Avoiding Regions Symptomatic of Conformational and Functional Flexibility to Identify Antiviral Targets in Current and Future Coronaviruses

2016 ◽  
Vol 8 (11) ◽  
pp. 3471-3484 ◽  
Author(s):  
Jordon Rahaman ◽  
Jessica Siltberg-Liberles
Keyword(s):  
Secondary Structure ◽  
Structure Prediction ◽  
Secondary Structure Prediction ◽  
Nonstructural Protein ◽  
Intrinsic Disorder ◽  
Sequence Motif ◽  
Protein Families ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Antiviral Targets

Abstract Within the last 15 years, two related coronaviruses (Severe Acute Respiratory Syndrome [SARS]-CoV and Middle East Respiratory Syndrome [MERS]-CoV) expanded their host range to include humans, with increased virulence in their new host. Coronaviruses were recently found to have little intrinsic disorder compared with many other virus families. Because intrinsically disordered regions have been proposed to be important for rewiring interactions between virus and host, we investigated the conservation of intrinsic disorder and secondary structure in coronaviruses in an evolutionary context. We found that regions of intrinsic disorder are rarely conserved among different coronavirus protein families, with the primary exception of the nucleocapsid. Also, secondary structure predictions are only conserved across 50–80% of sites for most protein families, with the implication that 20–50% of sites do not have conserved secondary structure prediction. Furthermore, nonconserved structure sites are significantly less constrained in sequence divergence than either sites conserved in the secondary structure or sites conserved in loop. Avoiding regions symptomatic of conformational flexibility such as disordered sites and sites with nonconserved secondary structure to identify potential broad-specificity antiviral targets, only one sequence motif (five residues or longer) remains from the >10,000 starting sites across all coronaviruses in this study. The identified sequence motif is found within the nonstructural protein (NSP) 12 and constitutes an antiviral target potentially effective against the present day and future coronaviruses. On shorter evolutionary timescales, the SARS and MERS clades have more sequence motifs fulfilling the criteria applied. Interestingly, many motifs map to NSP12 making this a prime target for coronavirus antivirals.

scholarly journals Insights into the Roles of the Sideroflexins/SLC56 Family in Iron Homeostasis and Iron-Sulfur Biogenesis

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 103
Author(s):  
Nesrine Tifoun ◽  
José M. De las Heras ◽  
Arnaud Guillaume ◽  
Sylvina Bouleau ◽  
Bernard Mignotte ◽  
...  
Keyword(s):  
Iron Homeostasis ◽  
Current Knowledge ◽  
Research Field ◽  
Molecular Function ◽  
Inner Mitochondrial Membrane ◽  
Iron Sulfur Cluster ◽  
Iron Sulfur ◽  
Mitochondrial Transporter ◽  
Mitochondrial Functions ◽  
Few Data

Sideroflexins (SLC56 family) are highly conserved multi-spanning transmembrane proteins inserted in the inner mitochondrial membrane in eukaryotes. Few data are available on their molecular function, but since their first description, they were thought to be metabolite transporters probably required for iron utilization inside the mitochondrion. Such as numerous mitochondrial transporters, sideroflexins remain poorly characterized. The prototypic member SFXN1 has been recently identified as the previously unknown mitochondrial transporter of serine. Nevertheless, pending questions on the molecular function of sideroflexins remain unsolved, especially their link with iron metabolism. Here, we review the current knowledge on sideroflexins, their presumed mitochondrial functions and the sparse—but growing—evidence linking sideroflexins to iron homeostasis and iron-sulfur cluster biogenesis. Since an imbalance in iron homeostasis can be detrimental at the cellular and organismal levels, we also investigate the relationship between sideroflexins, iron and physiological disorders. Investigating Sideroflexins’ functions constitutes an emerging research field of great interest and will certainly lead to the main discoveries of mitochondrial physio-pathology.

scholarly journals Insights Into the Roles of the Sideroflexins / SLC56 Family in Iron Homeostasis and Iron-Sulfur Biogenesis

2020 ◽  
Author(s):  
Nesrine Tifoun ◽  
José M. De las Heras ◽  
Arnaud Guillaume ◽  
Sylvina Bouleau ◽  
Bernard Mignotte ◽  
...  
Keyword(s):  
Iron Homeostasis ◽  
Current Knowledge ◽  
Research Field ◽  
Molecular Function ◽  
Inner Mitochondrial Membrane ◽  
Iron Sulfur Cluster ◽  
Iron Sulfur ◽  
Mitochondrial Transporter ◽  
Mitochondrial Functions ◽  
Few Data

Sideroflexins (SLC56 family) are highly conserved multi-spanning transmembrane proteins inserted in the inner mitochondrial membrane in eukaryotes. Few data are available on their molecular function but, since their first description, they were thought to be metabolite transporters probably required for iron utilization inside the mitochondrion. Such as numerous mitochondrial transporters, sideroflexins remain poorly characterized. The prototypic member SFXN1 has been recently identified as the previously unknown mitochondrial transporter of serine. Nevertheless, pending questions on the molecular function of sideroflexins remain unsolved, especially their link with iron metabolism. Here, we review the current knowledge on sideroflexins, their presumed mitochondrial functions and the sparse - but growing - evidence linking sideroflexins to iron homeostasis and iron-sulfur cluster biogenesis. Since an imbalance in iron homeostasis can be detrimental at the cellular and organismal levels, we also investigate the relationship between sideroflexins, iron and physiological disorders. Investigating Sideroflexins’ functions constitutes an emerging research field of great interest and will certainly lead to main discoveries on mitochondrial physiopathology.

A Systematic Review on Popularity, Application and Characteristics of Protein Secondary Structure Prediction Tools

2019 ◽  
Vol 16 (2) ◽  
pp. 159-172 ◽  
Author(s):  
Elaheh Kashani-Amin ◽  
Ozra Tabatabaei-Malazy ◽  
Amirhossein Sakhteman ◽  
Bagher Larijani ◽  
Azadeh Ebrahim-Habibi
Keyword(s):  
Systematic Review ◽  
Secondary Structure ◽  
Structure Prediction ◽  
Web Of Science ◽  
Secondary Structure Prediction ◽  
Structural Information ◽  
Protein Secondary Structure ◽  
Structural Features ◽  
Prediction Tools ◽  
Insight Into

Background: Prediction of proteins’ secondary structure is one of the major steps in the generation of homology models. These models provide structural information which is used to design suitable ligands for potential medicinal targets. However, selecting a proper tool between multiple Secondary Structure Prediction (SSP) options is challenging. The current study is an insight into currently favored methods and tools, within various contexts. Objective: A systematic review was performed for a comprehensive access to recent (2013-2016) studies which used or recommended protein SSP tools. Methods: Three databases, Web of Science, PubMed and Scopus were systematically searched and 99 out of the 209 studies were finally found eligible to extract data. Results: Four categories of applications for 59 retrieved SSP tools were: (I) prediction of structural features of a given sequence, (II) evaluation of a method, (III) providing input for a new SSP method and (IV) integrating an SSP tool as a component for a program. PSIPRED was found to be the most popular tool in all four categories. JPred and tools utilizing PHD (Profile network from HeiDelberg) method occupied second and third places of popularity in categories I and II. JPred was only found in the two first categories, while PHD was present in three fields. Conclusion: This study provides a comprehensive insight into the recent usage of SSP tools which could be helpful for selecting a proper tool.

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