清华大学：《分子生物学》课程PPT教学课件（基因ene）第八章 蛋白质定位（Protein localization）

Chapter 8 Protein localization 清第大当

Chapter 8 Protein localization

8.1 Introduction 8.2 Chaperones may be required for protein folding 8.3 Post-translational membrane insertion depends on leader sequences 8.4 A hierarchy of sequences determines location within organelles 8.5 Signal sequences initiate translocation 8.6 How do proteins enter and leave membranes? 8.7 Anchor signals are needed for membrane residence 8.8 Bacteria use both co-translational and post-translational translocation 8.9 Pores are used for nuclear ingress and egress 8.10 Protein degradation by proteasomes 清苇大当

8.1 Introduction 8.2 Chaperones may be required for protein folding 8.3 Post-translational membrane insertion depends on leader sequences 8.4 A hierarchy of sequences determines location within organelles 8.5 Signal sequences initiate translocation 8.6 How do proteins enter and leave membranes? 8.7 Anchor signals are needed for membrane residence 8.8 Bacteria use both co-translational and post-translational translocation 8.9 Pores are used for nuclear ingress and egress 8.10 Protein degradation by proteasomes

8.1 Introduction Leader of a protein is a short N-terminal sequence responsible for passage into or through a membrane. 清莘大学

Leader of a protein is a short N-terminal sequence responsible for passage into or through a membrane. 8.1 Introduction

8.1 Introduction Secreted protein Figure 8.1 Overview:proteins that are localized post-translationally are Plasma membrane proteir released into the cytosol after synthesis on free ribosomes.Some have signals Coated vesicle transpor for targeting to organelles such as the nucleus or mitochondria.Proteins that are localized cotranslationally associate C≥Golgi retention with the ER membrane during synthesis proteins ER retention signa so their ribosomes are "membrane Mitochondrial signal bound".The proteins pass into the endoplasmic reticulum,along to the Golgi,and then through the plasma ree ribosom embranous membrane,unless they have signals that cause retention at one of the steps on the pathway.They may also be directed Nuclear signal to other organelles,such as endosomes or lysosomes 清菜大兰 Post-translational transport Co-translational transport

Figure 8.1 Overview: proteins that are localized post-translationally are released into the cytosol after synthesis on free ribosomes. Some have signals for targeting to organelles such as the nucleus or mitochondria. Proteins that are localized cotranslationally associate with the ER membrane during synthesis, so their ribosomes are "membrane￾bound". The proteins pass into the endoplasmic reticulum, along to the Golgi, and then through the plasma membrane, unless they have signals that cause retention at one of the steps on the pathway. They may also be directed to other organelles, such as endosomes or lysosomes. 8.1 Introduction

8.1 Introduction ↓ weoe.co ↓ Organelle Signal Type Signal location length Mito chondrion N-terminal Amphipathic helix 12-30 Chloroplast N-terminal Charged >25 Nucleus Internal Basic or bipartite 7-9 Peroxisome C-terminal SKL 3 Figure 8.2 Proteins synthesized on free ribosomes in the cytosol are directed after their release to specific destinations by short signal motifs 清菜大当

Figure 8.2 Proteins synthesized on free ribosomes in the cytosol are directed after their release to specific destinations by short signal motifs. 8.1 Introduction

Plasma membrane 8.1 Introduction Lysosome■Golgh" Mannose-6-phosphate C-terminal KDEL Figure 8.3 Membrane-bound ribosomes have proteins ■■■ with N-terminal sequences that enter the ER during N-teminal signal sequence is cleaved synthesis.The proteins may Endoplasmic reticulum flow through to the plasma membrane or may be Cytosol diverted to other destinations by specific signals. 清苇大当

Figure 8.3 Membrane-bound ribosomes have proteins with N-terminal sequences that enter the ER during synthesis. The proteins may flow through to the plasma membrane or may be diverted to other destinations by specific signals. 8.1 Introduction

8.2 Chaperones may be required Protein acquires confom ation after for protein folding membrane passage 通 Protein must pass through channel in m emhrane Figure 8.4 A protein is constrained to a Folded confom ation narrow passage as it could prevent passage through membrane crosses a membrane. 情華大当

Figure 8.4 A protein is constrained to a narrow passage as it crosses a membrane. 8.2 Chaperones may be required for protein folding

8.2 Chaperones may be required for protein folding System Function Hsp70 Hsp70 (DnaK) ATPase Hsp40 (DnaJ) stimulates ATP ase GrpE (GrpE) Nucleotide exchange factor Chaperonin Hsp60 (GroEL) Foms two heptameric rings; Hsp10 (GroES) Fomms cap Figure 8.5 Chaperone families have eukaryotic and bacterial counterparts (named in parentheses). 清第大当

Figure 8.5 Chaperone families have eukaryotic and bacterial counterparts (named in parentheses). 8.2 Chaperones may be required for protein folding

8.3 The Hsp70 family is ubiquitous GrpE ATPATP→ADP.AF DnaJ DnaK Figure 8.6 DnaJ assists the binding of DnaK (Hsp70),which assists the folding of nascent proteins.ATP hydrolysis drives conformational change.GrpE displaces the ADP;this causes the chaperones to be released.Multiple cycles of association and dissociation may occur during the folding of a substrate protein. 清菜大当

Figure 8.6 DnaJ assists the binding of DnaK (Hsp70), which assists the folding of nascent proteins. ATP hydrolysis drives conformational change. GrpE displaces the ADP; this causes the chaperones to be released. Multiple cycles of association and dissociation may occur during the folding of a substrate protein. 8.3 The Hsp70 family is ubiquitous

8.4 Hsp60/GroEL Pr otein enters throu gh forms an en d of cylinder oligomeric ring structure Figure 8.7-1 A protein may be sequestered within a controlled environment for folding or Protein interacts only degradation. with walls of cavity 清苇大兰

Figure 8.7-1 A protein may be sequestered within a controlled environment for folding or degradation. 8.4 Hsp60/GroEL forms an oligomeric ring structure