DNA-based synthetic DNA-based synthetic lectins lectins to inv to - - PowerPoint PPT Presentation

▶

Apr 11, 2024 369 likes •482 views

DNA-based synthetic DNA-based synthetic lectins lectins to inv to investigate estigate clathrin clathrin- independent endocytosis independent endocytosis R.E. Ducker Illustration Chemical biology of membranes and therapeutic deliv Chemical

SLIDE 1

DNA-based synthetic DNA-based synthetic lectins lectins to inv to investigate estigate clathrin clathrin- independent endocytosis independent endocytosis

02/25/15 Unit seminar- Tiomas Murarasu 5

Chemical biology of membranes and therapeutic deliv Chemical biology of membranes and therapeutic deliver ery - U1143 INSERM/UMR3666 CNRS y - U1143 INSERM/UMR3666 CNRS

R.E. Ducker Illustration

SLIDE 2

02/25/15% Unit%seminarC%Thomas%Murarasu% 6%

! Clathrin and adaptors recruit cargos ! Polymerization triggers membrane deformation

MBInfo Wiki

Clathrin Clathrin dependent dependent endocytosis endocytosis mechanisms mechanisms

SLIDE 3

02/25/2015% Unit%SeminarC%Thomas%Murarasu% 7%

Nature Cell Biology 2014 Nature 2007

Evidence of uncoated vidence of uncoated vesicules esicules : : Clathrin Clathrin independent independent endocytosis endocytosis

Clathrin dependent : Clathrin independent :

SLIDE 4

02/25/2015% Unit%SeminarC%Thomas%Murarasu% 8%

A div A diversity of ersity of clathrin clathrin independent pathways for a v independent pathways for a variety of ariety of functions functions

SLIDE 5

In the case of

n the case of clathrin clathrin independent endocytosis : independent endocytosis : – H How cargos ar w cargos are r e recr ecruited uited – By which mechanisms membrane deformation and y which mechanisms membrane deformation and bending occurs bending occurs Major questions in membrane biology ajor questions in membrane biology

02/25/2015 %% Unit%SeminarC%Thomas%Murarasu% 9%

SLIDE 6

02/25/2015 Unit Seminar- Thomas Murarasu 10

Shiga to higa toxin as a model to study xin as a model to study clathrin clathrin independent independent endocytosis endocytosis

Johannes & W. Römer, Nature Reviews Microbiology 8, 105-116, 2010

GB3, natural ligand of GB3, natural ligand of STxB STxB

StxA StxB

Shiga higa Toxin xin str structur ucture e Pentameric entameric STxB STxB

SLIDE 7

02/25/2015 Unit Seminar- Thomas Murarasu 11

Römer et al., Nature, 2007

A pr A proposed model based on the

posed model based on the pentameric

pentameric str structur ucture of the e of the pr protein

tein

Shiga-GB3 Cholera-GM1 VP1-GM1

Hypothesis : a molecular arrangement shar ypothesis : a molecular arrangement shared among di ed among difg fger erent ent lectins lectins leads to membrane deformation leads to membrane deformation A mechanism shar A mechanism shared b ed by endogenous y endogenous lectins lectins (e.g. (e.g. Galectins alectins) )

Ti Tie pr e protein clustering leads to membrane

tein clustering leads to membrane

bending bending A stackable A stackable pentameric pentameric str structur ucture e

SLIDE 8

DNA N DNA Nanotechnologies : DNA based nanostr anotechnologies : DNA based nanostructur uctures principles es principles

02/25/2015% Unit%SeminarC%Thomas%Murarasu% 12%

DNA%properNes% RaNonal%Design% 2D%and%3D%nanostructures% FuncNonalizaNon%

SLIDE 9

Design of DNA-based synthetic esign of DNA-based synthetic lectins lectins

02/25/2015 Unit Seminar - Thomas Murarasu 13

1- Stoichiometry 2- Distance 3- Angle STxB STxB DNA-based synthetic DNA-based synthetic lectins lectins

Monomeric CRD DNA oligo

SLIDE 10

Biomedical A iomedical Application : pplication : Tumor cells speci umor cells specifj fjc targeting c targeting

GSLs%are%overexpressed%in%a%certain%number%of%cancer%Cells%(GBM1,%GD2,%GB3…)% An%heteropentamer%specifically%bind%and%enter%those%cells%

SLIDE 11