Group-specific component (Gc) proteins bind vitamin D and 25-hydroxyvitamin D.

Daiger, Stephen P.; Schanfield, Mel S.; Cavalli-Sforza, Luca

doi:10.1073/pnas.72.6.2076

Cited by 350 publications

(171 citation statements)

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“…The group-specific component (Gc), now established to be the binding protein for vitamin D (Daiger et al, 1975), is one of the serum proteins which show genetic polymorphism in human populations. Since Hirschfeld (1959) first discovered three common phenotypes, Gcl-1, Gc2-1 and Gc2-2, this Gc system has been utilized as a useful genetic marker for anthropological studies and in the field of forensic medicine.…”

Section: Introductionmentioning

confidence: 99%

Group-specific component (Gc) polymorphism in Japanese: An investigation on the phenotypic distribution with regard to theGc J allele

1978

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Section: Introductionmentioning

confidence: 99%

Group-specific component (Gc) polymorphism in Japanese: An investigation on the phenotypic distribution with regard to theGc J allele

1978

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“…In addition to its role as part of the actin-scavenger system, DBP is the main protein involved in the transport of vitamin D (11), hence its name. It is now well established, however, that less than 5% of circulating DBP is actually complexed with vitamin D metabolites, leaving a considerable amount of the protein available for other functions.…”

mentioning

confidence: 99%

Crystal structures of the vitamin D-binding protein and its complex with actin: Structural basis of the actin-scavenger system

Otterbein

Cosio

Graceffa

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

150

121

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Actin is the most abundant protein in eukaryotic cells, but its release from cells into blood vessels can be lethal, being associated with clinical situations including hepatic necrosis and septic shock. A homeostatic mechanism, termed the actin-scavenger system, is responsible for the depolymerization and removal of actin from the circulation. During the first phase of this mechanism, gelsolin severs the actin filaments. In the second phase, the vitamin Dbinding protein (DBP) traps the actin monomers, which accelerates their clearance. We have determined the crystal structures of DBP by itself and complexed with actin to 2.1 Å resolution. Similar to its homologue serum albumin, DBP consists of three related domains. Yet, in DBP a strikingly different organization of the domains gives rise to a large actin-binding cavity. After complex formation the three domains of DBP move slightly to ''clamp'' onto actin subdomain 3 and to a lesser extent subdomain 1. Contacts between actin and DBP throughout their extensive 3,454-Å 2 intermolecular interface involve a mixture of hydrophobic, electrostatic, and solventmediated interactions. The area of actin covered by DBP within the complex approximately equals the sum of those covered by gelsolin and profilin. Moreover, certain interactions of DBP with actin mirror those observed in the actin-gelsolin complex, which may explain how DBP can compete effectively with gelsolin for actin binding. Formation of the strong actin-DBP complex proceeds with limited conformational changes to both proteins, demonstrating how DBP has evolved to become an effective actin-scavenger protein.

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“…Vitamin D 3 bound to DBP is carried to the liver and hydroxylated at position 25 by CYP2R1 or CYP27A1, belonging to the cytochrome P450 (CYP) superfamily, resulting in 25-hydroxyvitamin D 3 (25D 3 ). 25D 3 binds to DBP and circulates through the blood; in the kidney, it binds to megalin, is highly expressed in the renal proximal tubule, and is taken up by endocytosis [1]. 25D 3 incorporated into cells together with DBP is hydroxylated at the 1α position by CYP27B1, resulting in 1α,25-dihydroxyvitamin D 3 (1α,25D 3 ).…”

Section: Commentarymentioning

confidence: 99%