What is the Difference Between Alpha and Beta Tubulin

The main difference between alpha and beta tubulin is that the alpha tubulin is almost completely detyrosinated but, only ~10% of the beta tubulin is phosphorylated. Furthermore, detyrosination refers to a form of post-translational modification which occurs on alpha tubulin while the phosphorylation of beta tubulin occurs on Ser441 in the C-terminal domain. Moreover, GTP always binds to alpha tubulin while GTP of beta tubulin tends to exchange with microfilaments.

Alpha and beta tubulin are the two main components of microtubules, which are highly heterogeneous molecules responsible for making cytoskeletal structures while involving in a number of cellular processes including mitosis, ciliary and flagellar motility, intracellular transport, and defining of cell morphology and polarity.

Key Areas Covered

1. What is Alpha Tubulin
     – Definition, Structure, Role
2. What is Beta Tubulin
     – Definition, Structure, Role
3. What are the Similarities Between Alpha and Beta Tubulin
     – Outline of Common Features
4. What is the Difference Between Alpha and Beta Tubulin
    – Comparison of Key Differences

Key Terms

Alpha Tubulin, Beta Tubulin, Cytoskeleton, GTP, Lysine, Microfilament, Microtubule, Post Translational Modifications

What is Alpha Tubulin

Alpha tubulin is one of the two protein components of a microtubule which plays a critical role in the formation of the cytoskeleton. Also, microtubules participate in several cellular events including cell division. Generally, both alpha tubulin and beta tubulin, which is the second protein component of a microtubule, are globular proteins comprising of three functional domains. They are the N-terminal domain, intermediate domain, and the C-terminal domain. Here, the N-terminal domain is made up of five alpha helices and six parallel beta strands, forming a Rossman fold. A GTP molecule sits at the base of the N-terminal domain.

Figure 1: Microtubule Structure

On the other hand, the intermediate domain is made up of three alpha helices, beta sheets, and two more helices. It forms a taxol binding domain. Usually, taxol is a ligand responsible for stabilizing the sheets against cold temperature depolymerization and ageing. However, the C-terminal is entirely made up of alpha helices and is responsible for the formation of a protofilament ‘crest’, overlapping other the other two domains. It allows the binding of other associated proteins and motor proteins to the microtubules.

Figure 2: Alpha and Beta Tubulin Structure

Furthermore, the main importance of alpha tubulin in a microtubule is that it provides a site for the binding of a GTP molecule. This GTP is hydrolyzed to GDP once the tubulin dimer is added to the plus end. Also, the hydrolysis of GTP occurs at the E site of the alpha tubulin. This hydrolysis is facilitated by the aspartate residue, which occurs at the 254^th amino acid position.

What is Beta Tubulin

As mentioned before, beta tubulin is the second protein component of the microtubule. It contains a lysine residue in its 254^th amino acid position. Lysine is responsible for strengthening the monomer-monomer interaction by interacting with the GTP phosphate group at N-site. Therefore, beta tubulin helps in stabilizing the structure of the microtubule. Furthermore, apart from the N-terminal domain, a GTP molecule can bind to the E (exchangeable) site of a tubulin molecule. However, the GTP in the beta tubulin is exchangeable for the polymerization of microfilaments.

Similarities Between Alpha and Beta Tubulin

• Alpha and beta tubulin are the two main structural components of microtubules.
• They are globular proteins.
• Also, both their molecular mass is around 50 kDa.
• Moreover, the structure of both alpha and beta tubulin is similar as both molecules have 40% sequence homology.
• Besides, their structure contains alpha helices, beta sheets, and random coils.
• Their monomer structure is formed by two interacting β sheets surrounded by α helices.
• Additionaly, they mainly occur in eukaryotes while prokaryotes have some related proteins to tubulin.
• Furthermore, both types of proteins undergo post-translational modifications.
• And, GTP provides the energy required by the polymerization of tubulins to form a microtubule.

Difference Between Alpha and Beta Tubulin

Definition

Alpha tubulin refers to one of the two protein components of a microtubule attached to GTP while beta tubulin is the second protein component of a microtubule. Thus, this is the fundamental difference between alpha and beta tubulin.

Structure

Alpha tubulin is made up of 13% alpha helices, 39% beta sheets, and 48% random coils while beta tubulin is made up of 13% alpha helices, 42% beta sheets, and 45% random coils. Thus, the structure is an important difference between alpha and beta tubulin.

254^th Amino Acid

Moreover, one other difference between alpha and beta tubulin is that the alpha tubulin contains aspartate as the 254^th amino acid while beta tubulin contains lysine as the 254^th amino acid.

The function of the 254^th Amino Acid

Also, the function of 254th amino acid also makes a difference between alpha and beta tubulin. The 254^th amino acid of alpha tubulin serves as an ideal residue for the hydrolysis of the nucleotide at the E-site while the 254^th amino acid of beta tubulin strengthens the monomer-monomer interaction by interacting with the GTP phosphate group at N-site.

GTP Binding

Furthermore, GTP is always attached to the alpha subunit while at the β subunit, GTP is exchangeable for the microfilaments to polymerize. Hence, this is another difference between alpha and beta tubulin.

Post Translational Modifications

Above all, the main difference between alpha and beta tubulin is that the alpha tubulin is almost completely detyrosinated whereas ~10% of the beta tubulin is phosphorylated.

Nature of Post Translational Modifications

Stemming from the above difference, detyrosination is responsible for the removal of the C-terminal tyrosine to expose glutamate at the newly formed C-terminus of alpha tubulin while the phosphorylation of beta tubulin occurs on Ser441 in the C-terminal domain. So, this is also a difference between alpha and beta tubulin.

Conclusion

Alpha tubulin is one of the two protein components of a microtubule. It is a globular protein almost completely detyrosinated as a post translational modification. Also, the GTP bound to the alpha tubulin is responsible for providing energy for the polymerization of tubulin. On the other hand, beta tubulin is the second protein component of a microtubule. Also, it is a globular protein sometimes undergoes phosphorylation. The main function of beta tubulin is to strengthen monomer-monomer interactions. Therefore, the main difference between alpha and beta tubulin is the structure and function.

References:

1. Lee, Young Jun. “Αβ Tubulin (PDB ID: 1jff) from Bos Taurus.” aB_tubulin, Available Here.
2. EMBL-EBI, InterPro. “Beta Tubulin (IPR002453).” InterPro, EMBL-EBI, Available Here.
3. “Tubulin.” Tubulin – an Overview | ScienceDirect Topics, Available Here.

Image Courtesy:

1. “Microtubule structure” By Thomas Splettstoesser (www.scistyle.com) – Own work (rendered with Maxon Cinema 4D) (CC BY-SA 4.0) via Commons Wikimedia   
2. “Tubulin dimer 1JFF” By Thomas Splettstoesser (www.scistyle.com) – Own work (rendered with Maxon Cinema 4D) (CC BY-SA 4.0) via Commons Wikimedia