【生命科学部】バイオフォーラムを開催します！（9月6日）
2024.08.09
最先端の生命科学研究に触れてみませんか
京都産業大学生命科学部では、ご活躍されている研究者をお招きし、生物学・生命科学に関する講演会「京都産業大学生命科学部バイオフォーラム」を不定期で開催しています。最先端の研究領域に触れる機会を提供することにより、学生・大学院生・教員の学習・研究意欲の向上及び学部・大学院の活性化を図ることを目的としています。
今回は以下のとおり3講演実施します！
- Alexander Mankin博士（シカゴ大学イリノイ校），Nora Vázquez-Laslop 博士 (シカゴ大学イリノイ校)
【テーマ】
A Fully-Integrated Protein Synthesis Machine (Mankin博士)
A Lasso-Peptide Inhibitor of the Bacterial Ribosome（Vázquez-Laslop 博士） - Prof. Ramanujan Hegde（MRC Laboratory of Molecular Biology, Cambridge, UK）
【テーマ】
Insertion and assembly of multipass membrane proteins - Prof. Tom A. Rapoport（Harvard Medical School and Howard Hughes Medical Institute, Boston, MA, US）
【テーマ】
Mechanism of protein import into peroxisomes
一般の方にも生命科学の最先端の研究に触れるいただける機会となります。ぜひ、ご参加ください！
| 日時 | 2024年9月6日（金）13：30～17：00
|
|---|---|
| 場所 | 京都産業大学 15号館1階15102セミナー室 キャンパスマップ |
| 交通 | ※キャンパス内に駐車場はありません。公共交通機関をご利用ください。 交通アクセス |
| 備考 | 事前申込不要・入場無料 |
| 主催 | 京都産業大学 生命科学部 |
講師
- Alexander Mankin博士（シカゴ大学イリノイ校）・Nora Vázquez-Laslop 博士 (シカゴ大学イリノイ校)
- Prof. Ramanujan Hegde （MRC Laboratory of Molecular Biology, Cambridge, UK）
- Prof. Tom A. Rapoport（Harvard Medical School and Howard Hughes Medical Institute, Boston, MA, US）
演題
- 「A Fully-Integrated Protein Synthesis Machine (Mankin博士)，A Lasso-Peptide Inhibitor of the Bacterial Ribosome（Vázquez-Laslop 博士）」
- 「Insertion and assembly of multipass membrane proteins」
- 「Mechanism of protein import into peroxisomes」
要旨
1. A Fully-Integrated Protein Synthesis Machine
Expanding ribosome functions to enable synthetic biology endeavors requires for the engineered ribosome to be functionally insulated from translating cellular proteins. Currently used approaches, that exploit complementarity between a specific mRNA and the16S rRNA of the engineered ribosome fail to achieve complete isolation. The wholly integrated translation system we are developing is aimed to achieve full orthogonality.
A Lasso-Peptide Inhibitor of the Bacterial Ribosome
Lasso peptides are ribosomally-synthesized and post-translationally modified peptides (RiPPs) with a distinct structurally constrained knotted fold. Many lasso peptides kill bacteria by disrupting cellular membranes or by acting upon intracellular targets. We have discovered the first lasso peptide whose antibiotic activity is based on binding to the ribosome and corrupting its ability to make proteins.
2. Our genomes encode ~3000 multipass membrane proteins. These proteins are essential for sensing the environment, communication with other cells, transport of nutrients and metabolites, neurotransmission, and countless other physiologic processes. Multipass membrane proteins inserted into the ER membrane are weaved back and forth multiple times across the lipid bilayer, folded into a functional three-dimensional structure, and sometimes assembled with other subunits. Our research aims to understand how such complex membrane proteins are made correctly. We have taken a biochemical approach to identify and mechanistically dissect the factors involved in membrane protein targeting, insertion, folding, and assembly. Work from our lab and others have defined a set of factors that are particularly important for multipass membrane protein insertion. This includes the targeting factor TMEM208, Oxa1-family insertases termed EMC and GEL, and an intramembrane chaperone complex termed PAT. I will discuss our current mechanistic understanding of how these factors operate and how their functions are coordinated with the Sec61 protein translocation channel. Our findings are leading to a unifying model for membrane protein biogenesis.
3. Peroxisomes are ubiquitous organelles whose dysfunction causes fatal human diseases. Most peroxisomal enzymes are imported in a folded state from the cytosol by the receptor PEX5. Recent work shows how PEX5 shuttles cargo into peroxisomes. PEX5 binds cargo in the cytosol and then enters peroxisomes by a process resembling nuclear transport. A meshwork is formed inside the membrane by a conserved tyrosine/glycine-rich YG domain of PEX13, and resembles the meshwork of nucleoporin FG domains inside nuclear pores. PEX5 selectively partitions into this phase, using conserved aromatic motifs, and brings bound cargo along. Directionality of import is probably determined by an interaction of PEX5 with a lumenal PEX14 domain. PEX5 returns to the cytosol through a retro-translocon formed by a ubiquitin ligase complex, consisting of PEX2, 10, and 12. The ligase complex has an open pore, into which the import receptors insert a flexible N-terminal segment from the lumenal side. Following mono-ubiquitination, PEX5 is pulled out of peroxisomes by the PEX1/6 ATPase. During retro-translocation, PEX5 is unfolded, which results in cargo release inside the organelle. After folding and deubiquitination, PEX5 can start a new import cycle.
※本講演は英語講演となります。通訳はありませんので，ご注意ください。
Expanding ribosome functions to enable synthetic biology endeavors requires for the engineered ribosome to be functionally insulated from translating cellular proteins. Currently used approaches, that exploit complementarity between a specific mRNA and the16S rRNA of the engineered ribosome fail to achieve complete isolation. The wholly integrated translation system we are developing is aimed to achieve full orthogonality.
A Lasso-Peptide Inhibitor of the Bacterial Ribosome
Lasso peptides are ribosomally-synthesized and post-translationally modified peptides (RiPPs) with a distinct structurally constrained knotted fold. Many lasso peptides kill bacteria by disrupting cellular membranes or by acting upon intracellular targets. We have discovered the first lasso peptide whose antibiotic activity is based on binding to the ribosome and corrupting its ability to make proteins.
2. Our genomes encode ~3000 multipass membrane proteins. These proteins are essential for sensing the environment, communication with other cells, transport of nutrients and metabolites, neurotransmission, and countless other physiologic processes. Multipass membrane proteins inserted into the ER membrane are weaved back and forth multiple times across the lipid bilayer, folded into a functional three-dimensional structure, and sometimes assembled with other subunits. Our research aims to understand how such complex membrane proteins are made correctly. We have taken a biochemical approach to identify and mechanistically dissect the factors involved in membrane protein targeting, insertion, folding, and assembly. Work from our lab and others have defined a set of factors that are particularly important for multipass membrane protein insertion. This includes the targeting factor TMEM208, Oxa1-family insertases termed EMC and GEL, and an intramembrane chaperone complex termed PAT. I will discuss our current mechanistic understanding of how these factors operate and how their functions are coordinated with the Sec61 protein translocation channel. Our findings are leading to a unifying model for membrane protein biogenesis.
3. Peroxisomes are ubiquitous organelles whose dysfunction causes fatal human diseases. Most peroxisomal enzymes are imported in a folded state from the cytosol by the receptor PEX5. Recent work shows how PEX5 shuttles cargo into peroxisomes. PEX5 binds cargo in the cytosol and then enters peroxisomes by a process resembling nuclear transport. A meshwork is formed inside the membrane by a conserved tyrosine/glycine-rich YG domain of PEX13, and resembles the meshwork of nucleoporin FG domains inside nuclear pores. PEX5 selectively partitions into this phase, using conserved aromatic motifs, and brings bound cargo along. Directionality of import is probably determined by an interaction of PEX5 with a lumenal PEX14 domain. PEX5 returns to the cytosol through a retro-translocon formed by a ubiquitin ligase complex, consisting of PEX2, 10, and 12. The ligase complex has an open pore, into which the import receptors insert a flexible N-terminal segment from the lumenal side. Following mono-ubiquitination, PEX5 is pulled out of peroxisomes by the PEX1/6 ATPase. During retro-translocation, PEX5 is unfolded, which results in cargo release inside the organelle. After folding and deubiquitination, PEX5 can start a new import cycle.
※本講演は英語講演となります。通訳はありませんので，ご注意ください。
