Membrane binding proteins

1. MEMBRANE BINDING PROTEINS:

2. WHAT ARE MEMBRANE BINDING PROTEINS?
Membrane binding proteins are common proteins that are part of ,or
interact with biological membrane.

3. STRUCTURAL FEATURE OF MEMBRANE BINDING PROTEINS:
• Membrane binding protiens have net positive charge.
• Contain large cationic patches.
• Contain more aliphatic and aromatic residues on the molecular surface.
• Have more stabilizing residues and less flexible residues on the surface
then non- binding one.

4. CLASSIFICATION OF MEMBRANE BINDING PROTEINS:
Based on structure ,three main classification of membrane binding
proteins:
1- Integral proteins.
2-peripheral proteins.
3-lipids anchored proteins.

5. DIFFERENT TYPES OF MEMBRANE BINDING PROTEINS:

6. 1- INTEGRAL OR INTRINSIC PROTEINS:
Permanently anchored to membrane or part of membranes.
Examples:
• Glycophorin
• Rhodopsin
• Band 3
• CD 36
• Glucose permease
• Ion channels and gates etc.

7. SUBCLASSES OF INTEGRATED MEMBRANE PROTEINS:
Two subclasses of integrated membrane proteins:
• Integral polytopic proteins.
• Integral monotonic proteins.

8. INTEGRAL POLYTOPIC PROTEINS:
• Also known as transmembrane proteins.
• Span across the membrane at least once.
• All transmembrane Proteins are integral membrane Proteins but not all
integral membrane Proteins are transmembrane proteins.
• These proteins have different topology which referred to orientation of
membrane spanning segments with respect to the inner and outer side
of biological membranes occupied by proteins.
• Examples: transmembrane alpha helix proteins, transmembrane beta
sheet proteins etc.

9. INTEGRAL MONOTOPIC PROTEINS:
Integral membrane proteins that are attached to only one side of
membrane and do not span the whole way across membrane .

10. BINDING MECHANISM OF INTEGRAL PROTEINS TO
MEMBRANE:
• Interact strongly with lipids bilayer in order to perform biological functions.
• Enzymatic processing of lipids and other hydrophobic substances.
• Membrane anchoring.
• Transferring of non polar compound between different cellular membrane.

11. Four types of binding interaction between monotopic integral
membrane Proteins and cell membrane.
1- Amphiphatical helix parallel.
2-Hydrophobic loop.
3-Covalently bound to membrane lipids.
4- Electrostatic or ionic interaction with membrane lipids.

12. DIFFERENT TYPES OF INTEGRAL MEMBRANE PROTEINS
STRUCTURE WITH RESPECT TO INTERACTION:

13. • Explanation of above figure:
1- A single transmembrane helix.
2- A polytopic transmembrane alpha helical protiens.
3- A polytopic transmembrane beta sheet protiens.
4-Interaction by an amphipathic alpha helix parallel to the membrane
plan.
5- Interaction by a hydrophobic loop.
6- Interaction by a covalently bound membrane lipids.
7-ionic or electrostatic interaction with membrane lipids.

14. FUNCTIONS OF INTEGRAL MEMBRANE PROTEINS:
1-Membrane receptors:
That embedded in the cell membranes,
which can transmit signals between the
cell internal and external environment.
Examples:
• Ion channels.
• G- proteins couples receptors.
• Various kind of transport proteins.

15. 2- Membrane transport proteins:
They transport ion, small molecules or
macromolecules across a biological membrane.
About membrane transporter there is a
detailed classification called transporter classification database
that’s approved by international Union of biochemistry
and molecular biology.
Example:
• Ion channels are one of the most important types
• of membrane transporter.

16. Function of ion channels include:
• Establishing a resting membrane potentials, action potentials and other
electrical signals by getting the flow of ions across cell membrane.
• Controlling the flow of ions across the secretory and epithelial cells.
• Regulation cell volume.

17. 3- Enzymes:
Various enzymes are integral membrane Proteins.
Example:
• Oxidoreductase
• Transferase
• Hydrolase

18. 4- Immunoglobulins:
Cell adhesion molecules that locate on the cell surface involve in binding with
other cells or with extracellular matrix allow cell to identify each other and
interact with outside molecules.
Example:
Proteins including Ig that’s superfamily involved in immune response.

19. 2 – PERIPHERAL MEMBRANE PROTEINS:
• Temporary attached to the lipids bilayer of membrane or other integral
proteins of membranes.
• Attached temporarily to the biological membrane with which they are
associated .
• Attached to the integral membrane Protiens or penetrate the
peripheral region of lipids bilayer.

21. MEMBRANE BINDING MECHANISM OF PERIPHERAL
MEMBRANE PROTEINS:
• The association of a proteins with lipids bilayer may involve Significant
changes with tertiary structure of proteins.
These may include :
• Folding of region of proteins structure that were previously unfolded
• Re- arrangement in the folding or refolding of the membrane associated part
of the proteins.
• Formation or dissociation of proteins quaternary structure and specific
binding of ions, ligands or regulatory lipids.
• Membrane binding affinity of many proteins depends on the specific lipids
composition of membrane with which they are associated .

23. CATEGORIES WITH FUNCTIONS:
1- Enzymes:
Peripheral enzymes participate in metabolism of different
membrane components, lipids , cell wall oligosaceides or
proteins.
Examples:
Lipases can also digest lipids that form micelles or non polar
droplet in water.

24. 2- Membrane Targeting domains:
Membrane targeting domains associated specifically with head group of their
lipids ligands embedded into the membrane.
Present in different concentrations in distinct types of biological membrane.
Example:
C1 domains binds diacylglycerol

25. 3 STRUCTURAL DOMAINS
Mediate attachment of other proteins to
membrane
Their binding to membrane can be
mediate by calcium ion that form bridges
between the acidic proteins residues and
phosphate group of lipids.
Example:
Annexins - carry membrane fusion and
ion channels formation.

26. 4- Transporters of small hydrophobic molecules:
Function as carrier of non- polar compound between different types of
cell membrane or between membrane and cytosolic protiens complex.
The transported substance are phosphatidylinositol, tocopherol,
Glycolipids, retinol, fatty acids, macromolecules, RBCs etc.
Example:
Glycolipids transfer proteins.

27. 5 ELECTRON CARRIER
Involve in the electron transport chain.
Example:
Cyt.C
Cupredouins
High potential iron proteins etc.

28. 6-polypeptide,harmonies,toxin and antimicrobial
peptides.
• Many hormones ,toxin, inhibitors or antimicrobial peptides interact
specifically with transmembrane proteins complex.
• They can also accumulate at the lipids bilayer surface ,prior to binding
their protein targets.
• They are positively charged and interact electrostatically with anionic
membrane.

29. 3 LIPIDS ANCHOR PROTEINS

30. • In lipid anchored proteins, a covalently attached fatty acid such as palmitate or myritate
serves to anchor them to either face of the cell membrane. Examples include G
proteins and certain kinases.
• Potential points of attachment include the terminal amino group of the protein backbone
and the side chain of cysteine residues

31. FUNCTIONS OF LIPIDS ANCHOR PROTEINS
• The lipid groups play a role in protein interaction and can contribute to the
function of the protein to which it is attached. Furthermore, the lipid serves as a
mediator of membrane associations or as a determinant for specific protein-
protein interactions. For example, lipid groups can play an important role in
increasing molecular hydrophobicity. This allows for the interaction of proteins
with cellular membranes and protein domain.

32. Thank you