human cardiac troponin in the Ca2+-saturated form
Homo sapiens (human)
All basic movements in animals require the rapid contraction of muscles. In vertebrates, voluntary movements, like running, walking, flying, are the result of skeletal muscle contractions, while non-voluntary movements like heart pumping are due to the rapid contraction of cardiac muscles. Skeletal muscles are made up of long muscle cells called muscle fibers. Each muscle fiber has multiple nuclei and cytoplasm that consists mainly of cylindrical structures called myofibrils. Myofibrils are the basic contractile elements of the muscle cell and are composed of a repeated chain of small contractile units called sarcomeres. Each sarcomere is an array of parallel ordered thick and thin filaments that slide over one another to achieve muscle contraction. The thick and thin filaments are composed of proteins called actin (see PDB:1ATN) and myosin (see PDB:1B7T) II, respectively. Muscle contraction is effected by changes in the levels of intracellular Ca2+. Ca2+ is regulated by the proteins, troponin and tropomyosin, both of which are located along the polymerized actin (thin) filament. In the resting state, under low levels of Ca2+, troponin binds to tropomyosin and prevents the sliding of the thick filament over the thin filament. At high levels of Ca2+, troponin binds to Ca2+ and releases tropomyosin allowing the movement of the thick filament over the thin filament and resulting in muscle contraction.
Troponin consists of 3 subunits -TnC, the Ca2+ binding subunit, TnI, the inhibitory subunit and TnT, the tropomyosin binding subunit. The structure presented here is that of the core domain of troponin complexed with Ca2+. The core domain consists of the TnC, TnI and a portion of TnT. It is structurally divided into two subdomains - the regulatory head and the IT arm. The regulatory head consists of the TnC and TnI subunits.The IT arm is a rigid alfa-helical coiled-coil formed by the TnT and TnI subunits. The regulatory head and the IT arm are connected by a flexible linker endowing troponin with a remarkable amount of flexibility that is important in its role in muscle contraction. The authors suggest that Ca2+ binding to TnC causes TnI to dissociate from actin resulting in a change in the flexibility of troponin and tropomyosin on the actin filament.
Protein Data Bank (PDB)
Takeda, S. Yamashita, A. Maeda, K. Maeda, Y.; "Structure of the core domain of human cardiac troponin in the Ca2+-saturated form"; Nature; (2003) 424:35-41 PubMed:12840750.
author: Ashwini Patil