Anatomy & Organs

Titin – structure, function & diseases

Titin

The elastic protein titin consists of around 30,000 amino acids , making it the largest known human protein.

As a component of the sarcomere , the smallest contractile unit of the skeletal and cardiac muscles , titin in the form of filaments ensures the elastic connection between the Z-discs and the myosin heads . Titin filaments are passively pre-tensioned and retract the myosin filaments after contraction, which is somewhat comparable to the function of a pre-tensioned return spring in a machine.

What is titin?

Titin is a comparatively huge, elastic protein with a molecular mass of about 3.6 million daltons, making it the largest known human protein molecule. Also known as connectin , titin is an important component of striated skeletal and cardiac muscle.

Stringed together, titin molecules combine to form elastic titin filaments and hold the myosin filaments in position in the sarcomere, the smallest contractile unit of muscle . After contraction and subsequent relaxation of the muscle, they support the repositioning of the myosin filaments through their elastic pretension. During the resting phase of the muscle, the titin filaments ensure sustained slight muscle tension.

According to the international rules of the “International Union of Pure and Applied Chemistry” (IUPAC), proteins are named after the amino acids they contain, namely according to their primary sequence. Applying this rule to Titin produces an acronym of nearly 190,000 letters that would take several hours to read.

Anatomy & Structure

Within a sarcomere, titin filaments provide the elastic connection between the contractile myosin filaments and the so-called Z-discs that bound each sarcomere at both ends.

Each individual myosin filament is connected at its end to a titin filament, which is anchored to the Z-disc so that the myosin filaments are held in the correct position by the titin filaments during the resting phase and also during the contraction phase. The approximately 30,000 amino acids are arranged in a total of 320 protein domains. Protein domains consist of a sequence of amino acids that can act as an independent protein or polypeptide and take on physiological functions independent of the rest of the protein molecule.

Several hundred sarcomeres connected in series form a muscle or myofibril, which in turn join together in several hundred to form a muscle fiber. Under the light microscope, the individual zones of the sarcomeres, which are arranged parallel and one behind the other, are visible as transverse stripes. The lighter so-called I-bands can be seen to the right and left of the dark Z-discs, which contain actin filaments and mainly elastic titin.

Function & Tasks

The contractile function of a sarcomere, the smallest functional unit within a striated muscle cell, is based on myosin filaments, which slide into one another during muscle contraction and thus cause the sarcomere to shorten. In order for the shortening of the myosin filaments to affect the entire muscle, they are connected to titin filaments on both sides, which in turn are anchored to the Z-discs.

This means that the titin filaments form an elastic connection between the myosin filaments and the Z-discs. The titin filaments ensure that the myosin filaments are held in a central position between the surrounding actin filaments, both in the relaxed and in the contracted state. The elasticity of the titin means that the contraction and relaxation phases of the muscle do not follow one another in a jerky manner, but are slowed down and can be better controlled with fine motor skills. In addition, the titin filaments counteract injury to the muscle fibers during strong and violent stretching by elastically “giving in”.

In addition, because the titin filaments also shorten during the contraction phase, increasing the contractile distance of the sarcomere, the titin filaments increase the total distance that a muscle can contract overall. During the relaxation phase of the muscle, the effect of the titin filaments is comparable to the working principle of a return spring due to their basic tension. The elasticity of the titin thus passively supports the work of the antagonistic muscle, which in principle ensures that the sarcomeres are “pulled” back to their original length.

Diseases

There are no known muscular diseases and complaints that could be attributed to a malfunction of the structural protein titin. The most well-known muscle complaint in which Titin also plays a role is sore muscles, which almost everyone is confronted with at one or more times in their lives.

According to recent findings, muscle soreness is caused by micro tears in the Z-discs of the sarcomere and the destruction of the support structures for titin and other proteins involved. It is very likely that the typical sore muscles are caused by a reaction of the muscle cells to the minor injuries. Painful inflammatory reactions develop, which should enable rapid repair of the sarcomeres. When it comes to sore muscles, there is still an opinion that the muscles are over-acidified with lactic acid , an assumption that has now been refuted.

Myasthenia gravis is a rare neuromuscular disease that also involves titin. It is a disorder of the motor signal transmission to the muscle cells. Autoantibodies block the acetylcholine receptors on the motor endplate. Autoantibodies are directed against the body’s own tissues or hormones . In most patients suffering from myasthenia gravis, antibodies against the protein fragment MGT30 can be detected.

It is a polypeptide with a molecular mass of 30,000 daltons that is contained in titin. The detection of antibodies against a partial structure of titin is used for differential diagnosis when the autoimmune disease myasthenia gravis is suspected to be present.

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Hello! I am Lisa Newlon, and I am a medical writer and researcher with over 10 years of experience in the healthcare industry. I have a Master’s degree in Medicine, and my deep understanding of medical terminology, practices, and procedures has made me a trusted source of information in the medical world.