BIOC 212 Lecture Notes - Lecture 6: Glycosylation, Acetyl Group, Secretion
28 May 2018
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2- Membrane Proteins
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Membrane Proteins
• Sequence of protein determines its structure, which implies function & localization
o Also for membrane proteins
o Sequence determines where are located in cell --true for soluble proteins as
well as membrane proteins
• Structure of membrane proteins involves added contacts with lipids in membrane
• Localization of membrane proteins requires protein-based targeting mechanisms
o Trafficking --> proteins that recognize the proteins and sort them according to
where need to be in the cell
• Terminology: soluble proteins are not associated with membranes (water-soluble)
o Membrane proteins on the other hand are physically associated with the
membrane
Integral Membrane Proteins
• Integrated in the membrane
• Integral membrane proteins are tightly anchored by hydrophobic interactions with
the interior of the lipid bilayer --> stick into hydrophobic center of lipid bilayer
• Different types of attachment
o 1+ transmembrane α-helices
• Multiple can cluster together
o Transmembrane β-barrel
• Beta sheet wrapping around in cylinder that crosses the membrane to
interact with membrane lipids
o Amphipathic α-helix in one face of the membrane
• Hydrophobic on one side, polar one the other
• Only inserted on one side of the helix
Lipid-Anchored & Peripheral Membrane Proteins
• Lipid-anchored: proteins are covalently linked to one or more lipids or fatty acid
groups
o Strength of anchor depends on number & type of lipid (how hydrophobic they
are)
o Lipid-attachment connects the proteins to the membrane
• Peripheral membrane proteins: attached by non-covalent interactions, but not
itself inserted in the hydrophobic part of the bilayer
o With integral membrane proteins, can be strong interactions
o With lipid head groups, weak interactions
• Come on & off fairly easily
• Lipid head groups are polar & charged
Transmembrane Helices (Integral membrane Proteins)
• Transmembrane a-helix is the most common form of attachment
• Like all a-helices, amino acid side chains point outwards
o In transmembrane helices, side chains are hydrophobic to interact with lipids
• Associate stably with inside of the bilayer (hydrophobic)
o Internal H-bonds maintain structure of helix (between each turn of helix)
• Segment sticking out into cytosol or lumen has polar side chains (aqueous)
Single & Multiple TM Helices
• Proteins can have 1 or more helical transmembrane domains
o Single-pass and multi-pass proteins
• TM helices longer, more hydrophobic than hydrophobic regions that form the
interior of a soluble protein
• Usually 18-24 aa long
• Can often be predicted from hydrophobicity of primary sequence
o When line up primary sequence of polypeptide, can scan along and identify
stretches of hydrophobicity
o If are hydrophobic enough and have enough of them in a row; can predict that
it is a transmembrane helix
• Plot hydrophobicity on scale
o See large region of hydrophobicity corresponding to TM helix in protein on the
left, and up to 7 on the right
o Segments are not the same length and the same degree of hydrophobicity
o Set threshold, that helps us make predictions
• Even though some amino acids are classified as hydrophobic (non-polar), have a
range of different chemical characteristics
Amino Acid Hydrophobicity index
• Can measure the relative hydrophobicity of amino acids
• This is scale based on free energy of partitioning from aqueous solution into some
organic solvent
o Assign numerical value to hydrophobicity
• Have range of hydrophobicity --> tryptophan is the most hydrophobic (largest)
o Tyrosine is quite hydrophobic, but has an OH group
• Need to get passed the classifications
• For interactions with the membrane, tyrosine is hydrophobic
• In terms of chemical reactions, it has hydroxyl group that can be
phosphorylated in the same way as a serine (polar uncharged)
TM Helices
• Length of TM helices matches the width of the membrane
o Hydrophobic region must be same width as the thickness of the membrane
Document Summary
Transmembrane helices (integral membrane proteins: transmembrane a-helix is the most common form of attachment, like all a-helices, amino acid side chains point outwards. In transmembrane helices, side chains are hydrophobic to interact with lipids: associate stably with inside of the bilayer (hydrophobic) Internal h-bonds maintain structure of helix (between each turn of helix: segment sticking out into cytosol or lumen has polar side chains (aqueous) In terms of chemical reactions, it has hydroxyl group that can be phosphorylated in the same way as a serine (polar uncharged) Tm helical structures: multiple tm helices can fold together into functional structures embedded in the membrane, are mostly hydrophobic, so tend to cluster together, cluster may assume different functions. If look from the face of the membrane (top) --the white in the middle is the aqueous pore and in green see the tm helices that surround the pore. Ion selectivity: channel pore contains selectivity filter for specific ion i. e. k+
