Question

Explain the different steps leading a 7 pass transmembrane receptor protein being exposed on the plasma membrane. You will start as the mRNA encoding for this protein was just exported outside of the nucleus.

Answer 1

• Transmembrane proteins are synthesized by bound ribosomes i.e. movement of protein occurs co translationaly.
• Synthesis of plasma membrane proteins occurs in endoplasmic reticulum.
• Translation of endoplasmic reticulum targeted protein is initiated in free ribosome in cytosol, growing peptide or nascent peptide contains N-terminal endoplasmic reticulum (ER) target signal.
• Endoplasmic target signal is recognised by the signal recognition particle (SRP).
• SRP binding to the peptide induces conformational change in the ribosome and translation is blocked for a small period of time this process is also known as elongation arrest.
• SRP receptor is present on membrane of endoplasmic reticulum, and is made up of α subunit which is peripheral and recognise SRP and β transmembrane subunit.
• SRP receptor is associated with the translocon channel known as sec 61 complex which is a trimer and is responsible for movement of translated protein into ER lumen.
• When SRP interacts with SRP receptor translation is re-initiated on the surface of endoplasmic reticulum.
• Sec 61 Complex directs the movement of protein into ER lumen. In ER lumen signal peptidase removes the N-terminal ER targeting signal sequence.
• Protein folding in ER lumen is assisted by proteins calnexin and calreticulin.
• From ER lumen target protein movement occurs by vesicular transport process. In this process a transport vesicle is produced from donor compartment which later fuses with the acceptor compartment which are mediated by COP II (from ER to Golgi, anterograde movement) and COP I (Golgi to ER, retrograde movement) Vesicles.
• Membrane proteins are retained in ER as they contain KKXX sequence at C terminal which are then first integrated on ER membrane and later by secretory pathway attached to plasma membrane.
• Plasma membrane proteins contain N-terminal target signal sequence which is removed in ER lumen, internal stop transfer signal and multiple stop and start transfer signals.