Membrane Proteins 10.2

10.2 Membrane Proteins: Structure and Basic Functions

Definition and Location

  • Membrane proteins are defined by their location within or at the surface of a phospholipid bilayer.

  • Every biological membrane has a basic bilayer structure, with the proteins associated with a specific membrane responsible for its unique activities.

Variation by Cell Type

  • The kinds and amounts of proteins in biomembranes vary depending on

    • Cell type

    • Subcellular location.

  • Inner mitochondrial membrane: 76% protein.

  • Myelin membrane (surrounds nerve axons): 18% protein. High phospholipid content allows electrical insulation.

Importance of Membrane Proteins

  • Approximately one-third of all yeast genes encode a membrane protein.

  • In multicellular organisms, the relative abundance of membrane protein genes is even higher, with ~7000 of ~20,000 genes in the human genome encoding membrane proteins.

  • Membrane proteins play essential roles in:

    • Cell adhesion

    • Communication between different cell types (cell-cell interactions).

Distinctive Environment

  • The lipid bilayer provides a unique two-dimensional hydrophobic environment for membrane proteins, influencing their structure and function.

  • Some proteins are embedded in the hydrophobic core of the lipid bilayer, while others associate with the exoplasmic or cytosolic leaflets of the bilayer.

Functions of Membrane Protein Domains

  • Extracellular surface domains bind to various molecules, including:

    • External signaling proteins

    • Ions

    • Small metabolites (e.g., glucose, fatty acids).

  • Membrane-spanning segments:

    • Form channels and pores for molecule and ion transport.

    • Organize multiple membrane proteins into larger assemblies.

  • Cytosolic face domains can anchor cytoskeletal proteins, trigger intracellular signaling pathways, or synthesize ATP.

Classification of Membrane Proteins

  • Membrane proteins are categorized into three types based on their position:

    1. Integral (transmembrane) proteins.

    2. Lipid-anchored proteins.

    3. Peripheral proteins.

Integral Membrane Proteins (Transmembrane Proteins)

  • Span the phospholipid bilayer and contain three domains:

    • Cytosolic domain: interacts with the aqueous cytosol.

    • Exoplasmic domain: interacts with the aqueous external environment.

    • Membrane-spanning segment: rich in hydrophobic amino acids interacting with the lipid core.

  • Structure:

    • Usually consists of one or more α helices or multiple β strands.

    • Amino acid composition resembles that of other water-soluble proteins.

Lipid-Anchored Membrane Proteins

  • Bound covalently to one or more lipid molecules.

  • The hydrophobic tail of the lipid is embedded in one leaflet of the membrane, anchoring the protein without entering the bilayer.

Peripheral Membrane Proteins

  • Do not contact the hydrophobic core.

  • Bound indirectly via interactions with integral or lipid-anchored proteins or directly with lipid head groups.

  • Can be located on either the cytosolic or exoplasmic face of the membrane.

  • Associated with cytoskeletal filaments providing cellular support and shape.

Interactions with Membranes

  • Membrane proteins must interact uniquely with the lipid bilayer, and their interaction mechanisms include:

    • Involvement of hydrophobic α helices for stability within membranes.

    • Understanding membrane topology can be predicted based on similarity with other characterized proteins.

Transmembrane Protein Structures

  • Characteristic structures for transmembrane proteins,

    • Dominance of hydrophobic α helices.

    • Typical length of α helices (20-25 hydrophobic amino acids) spanning the bilayer (approx. 3.75 nm).

  • Orientation:

    • Perpendicular or oblique angles to the plane of the membrane.

    • Formation of hydrogen bonds and hydrophobic interactions stabilizing structure.

Glycophorin A Example

  • Major protein in erythrocyte plasma membrane:

    • Contains a single membrane-spanning α helix.

    • Forms dimers, contributing to the coiled-coil structure.

Other Examples of Multipass Proteins

  • Integral proteins include those with seven membrane-spanning α helices (like G protein–coupled receptors) and bacteriorhodopsin, which illustrates light absorption and proton pumping for ATP synthesis.

Aquaporins

  • Large family of proteins facilitating the transport of water and glycerol across membranes.

  • Comprised of tetramers with six membrane-spanning α helices facing the bilayer; some helices do not span completely.

Specific Interactions

  • Phospholipid-protein interactions vary, influenced by the lipid tail length and structure.

  • Specificity of interactions underlies function and stability of membrane proteins within their environments.

Membrane Protein Removal and Study

  • Membrane proteins can be solubilized using

    • Detergents (ionic and non-ionic)

    • High-salt solutions.

  • Detergents can solubilize membrane-associated proteins while preserving protein structure:

    • Ionic detergents (e.g., SDS) denature proteins by disrupting ionic and hydrogen bonds.

    • Non-ionic detergents maintain protein structure and function during purification.

Blood Group Proteins Example (ABO Blood Group Antigens)

  • Determined by the presence of specific glycosyltransferases that add sugars to glycoproteins and glycolipids.

  • Blood type compatibility crucial for transfusions to prevent immune reactions due to antibody presence.

Overview of Membrane Protein Characteristics

  • Asymmetrically oriented in membranes.

  • Glycoproteins and glycolipids are abundant in the exoplasmic domain but absent in the inner mitochondrial membranes.

  • Carbohydrate chains extend into extracellular spaces facilitating interactions with various biological molecules.