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MEMBRANE SHAPING AND REMODELING BY PROTEINS. THANKS AND CREDIT :. COLLABORATION:. TEL AVIV GROUP:. HARVEY MCMAHON. ADI PICK. TOM RAPOPORT. FELIX CAMPELO. GUR FABRIKANT. WINFRIED WEISSENHORN. TOM SHEMESH. LEONID CHERNOMORDIK. INTRACELLULAR MEMBRANE - PowerPoint PPT Presentation
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MEMBRANE SHAPING AND REMODELING BY PROTEINS
THANKS AND CREDIT:
FELIX CAMPELO
HARVEY MCMAHONADI PICK
TEL AVIV GROUP: COLLABORATION:
TOM SHEMESH LEONID CHERNOMORDIK
WINFRIED WEISSENHORNGUR FABRIKANT
TOM RAPOPORT
h/R~ 0.2
Radius of curvature R ~ 20 nm is close to the monolayer thickness h ~ 4 nm
INTRACELLULAR MEMBRANE SHAPES AND DYNAMICS
VIRAL MEMBRANE DYNAMICS
THREE ESSENTIALLY DIFFERENT GEOMETRICAL TRANSFORMATIONSMEDIATING DYNAMIC SHAPING
BENDING (GENERATION OF CURVATURE) REMODELING BY FISSION OR FUSION (CHANGE OF MEMBRANE CONTINUITY,
AND MEMBRANE TOPOLOGY)
FISSION
FUSION
MEMBRANES RESISTS TO BOTH BENDING AND REMODELING
MEANING THAT
ENERGY HAS TO BE SUPPLIED BY SPECIAL PROTEINS
MEMBRANE RESISTENCE TO MEAN CURVATURE GENERATION:INVOLVED IN SHAPING AND REMODELING
POSITIVE CURVATURE NEGATIVE CURVATURE
BENDING STRESS
22
1scc JJw
BENDING ENERGY: HELFRICH MODEL
sc JJ
c BENDING (SPLAY) MODULUS
SPONTANEOUS CURVATURE
Tkerg Bc 10104 13
SJ
ENERGY OF GAUSSIAN CURVATURE (HELFRICH MODEL)
CHANGE OF MEMBRANE CONNECTIVITY (TOPOLOGY): INVOLVED IN REMODELNG
)1(4 pF
CONSIDERABLE ENERGY IS ASSOCIATED WITH THE FISSION EVENT
TkB5MODULUS OF GAUSSIAN CURVATURE
IN ADDITION, TRANSIENT MEMBRANE DISCONTINUITY REQUIRES ENERGY
)1(4 pdAwF K KwK
QUESTIONS TO ANSWER:
PHYSICS:MECHANISTIC PRINCIPLES OF MEMBRANE BENDING AND FUSION/FISSIONBY DIFFERENT PROTEINS BASED ON ENERGY CALCULATIONS.
BIOLOGY:WHETHER THESE PRINCIPLES ARE UNIVERSAL AND DETERMINE ACTION OF DIVERSEPROTEINS
BIOLOGY:WHETHER SAME PROTEINS CAN DRIVE BOTH FUSION AND FISSION
BIOLOGY:WHETHER SAME PROTEINS CAN BE USED TO DRIVE MEMBRANE BENDING AND REMODELING OR DIFFERENT PROTEINS ARE NEEDED
CURVATURE GENERATION BY LIPIDS
EFFICTIVE NON-BILAYER SHAPES OFLIPID MOLECULES
ASYMMETRY OF TWO MONOLAYERS:a. DIFFERENT NUMBERS OF LIPID MOLECULESb. DIFFERENT LIPID COMPOSITIONS
FOR BILAYER
ASYMMETRICAL STRUCTURE OF LIPID MOLECULES
FOR MONOLAYER
SPONTANEOUS CURVATURES OF REPRESENTATIVE LIPIDS(RAND AND FULLER)
X-rays measurements of lipid mesophases
P Rand (Brock Univ., Canada)
0sJLysophosphatidylcholine (LPC): 126.0
8.3
1 nmnm
J LPCs
Common Lipids:
Phosphatidylcholine (PC): 111.07.8
1 nmnm
J PCs
Lysolipids:
Hexagonal lipids
0sJ
0sJDioleoylPE (DOPE)
135.08.2
1 nmnm
J DOPEs
Diacylglycerol (DAG) 191.01.1
1 nmnm
J DOPEs
MECHANISMS OF MEMBRANE CURVATURE GENERATION BY DIRECT ACTION OF PROTEINS
HYDROPHOBIC INSERTION SCAFFOLDING
CAMPELO ET AL 2008 VOTH ET AL 2008
SYNAPTOTAGMIN(D.Z.HERRICK ET AL., 2006)
FUSION PEPTIDES
AMPHIPATHIC HELICES C2 DOMAINS
L. TAMM, BBA 2007
HYDROPHOBIC-INSERTION MECHANISM OF MEMBRANE BENDING
N-BAR DOMAINS N-BAR DOMAINS
SMALL G-PROTEINS
STRUCTURE
MODEL OF ACTION
HYDROPHOBIC INSERTION PROTEINS: EPSIN
TUBULATION OF PIP2 BILAYERS
D=20nm
SCAFFOLDING PROTEINS: BAR DOMAIN PROTEINS
EndophilinBAR
N-BAR
STRUCTURE MODEL OF ACTION
TUBULATION OF PS BILAYERS
D=20nm
STRUCTURE EHD2
MODEL OF ACTION
TUBULATION IN VIVO BY OVEREXPRESSION
OTHER TYPE OF SCAFFOLDING PROTEINS. EPSIN HOMOLOGY DOMAINS (EHD@)
TUBULATION OF PS BILAYERS
D=20nm
SMALL INCLUSION GENERATES ELASTIC DEFORMATION OF THE MONOLAYER MATRIX
SMALL HYDROPHOBIC INSERTION MECHANISM: QUALITATIVELY
MEMBRANE AS A THICK LAYER: RELEVANT SCALES ARE COMPARABLE WITH MEMBRANE THICKNESS
INTRA-MEMBRANE DISTRIBUTION OF STRESSES AND RIGITIES
from Illya, Lipowsky and Shillcock, J Chem Phys 122, 244901 (2005)σ
TRANS-MEMBRANE STRESS PROFILE
TRANS-MEMBRANE ELASTICITY PROFILE
λT
STRETCHING TRANSVERSE SHEAR
λS
dVuuudF lmikiklmikik )2
1(
λT λS
λ
COMPUTING MEMBRANE BENDING BY INSERTIONS
BEFORE INSERTIONDEFORMED STATE AFTER INSERTION
LOOKING FOR CONFORMATION OF MINIMAL ELASTIC ENERGY
FELIX CAMPELO
EFFECTIVE SPONTANEOUS CURVATURE OF INSERTION
Zinc/hMAXIMAL SPONT.CURV. FOR INCLUSION
ζinch ~ 0.75
MAXIMAL SPONT.CURV. FOR LIPID (LPC)
ζLPCh ~ 0.3
EFFECTIVE SPONTANEOUS CURVATURE OF INSERTION
0.05zinch
MEMBRANE TUBULATION BY N-BAR DOMAIN
SHALLOW HYDROPHOBIC INSERTIONS ARE MORE EFFECTIVE THEN LIPIDS
IN CURVATURE GENERATION
CURVATURE GENERATION BY SCAFFOLDING PROTEINS:
SHAPING OF ENDOPLASMIC RETICULUM