membrane shaping and remodeling by proteins
DESCRIPTION
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 PresentationTRANSCRIPT
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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
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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
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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
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MEMBRANES RESISTS TO BOTH BENDING AND REMODELING
MEANING THAT
ENERGY HAS TO BE SUPPLIED BY SPECIAL PROTEINS
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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
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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
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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
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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
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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
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MECHANISMS OF MEMBRANE CURVATURE GENERATION BY DIRECT ACTION OF PROTEINS
HYDROPHOBIC INSERTION SCAFFOLDING
CAMPELO ET AL 2008 VOTH ET AL 2008
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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
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STRUCTURE
MODEL OF ACTION
HYDROPHOBIC INSERTION PROTEINS: EPSIN
TUBULATION OF PIP2 BILAYERS
D=20nm
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SCAFFOLDING PROTEINS: BAR DOMAIN PROTEINS
EndophilinBAR
N-BAR
STRUCTURE MODEL OF ACTION
TUBULATION OF PS BILAYERS
D=20nm
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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
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SMALL INCLUSION GENERATES ELASTIC DEFORMATION OF THE MONOLAYER MATRIX
SMALL HYDROPHOBIC INSERTION MECHANISM: QUALITATIVELY
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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
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TRANS-MEMBRANE ELASTICITY PROFILE
λT
STRETCHING TRANSVERSE SHEAR
λS
dVuuudF lmikiklmikik )2
1(
λT λS
λ
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COMPUTING MEMBRANE BENDING BY INSERTIONS
BEFORE INSERTIONDEFORMED STATE AFTER INSERTION
LOOKING FOR CONFORMATION OF MINIMAL ELASTIC ENERGY
FELIX CAMPELO
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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
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0.05zinch
MEMBRANE TUBULATION BY N-BAR DOMAIN
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SHALLOW HYDROPHOBIC INSERTIONS ARE MORE EFFECTIVE THEN LIPIDS
IN CURVATURE GENERATION
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CURVATURE GENERATION BY SCAFFOLDING PROTEINS:
SHAPING OF ENDOPLASMIC RETICULUM