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pubmed-article:15161904pubmed:abstractTextVertebrate glycoprotein hormone heterodimers are stabilized by a strand of their beta-subunits known as the "seatbelt" that is wrapped around loop 2 of their alpha-subunits (alpha2). The cysteine that terminates the seatbelt is "latched" by a disulfide to a cysteine in beta-subunit loop 1 (beta1) of all vertebrate hormones except some teleost follitropins (teFSH), wherein it is latched to a cysteine in the beta-subunit NH(2) terminus. As reported here, teFSH analogs of human choriogonadotropin (hCG) are assembled by a pathway in which the subunits dock before the seatbelt is latched; assembly is completed by wrapping the seatbelt around loop alpha2 and latching it to the NH(2) terminus. This differs from hCG assembly, which occurs by threading the glycosylated end of loop alpha2 beneath the latched seatbelt through a hole in the beta-subunit. The seatbelt is the part of the beta-subunit that has the greatest influence on biological function. Changes in its sequence during the divergence of lutropins, follitropins, and thyrotropins and the speciation of teleost fish may have impeded heterodimer assembly by a threading mechanism, as observed when the hCG seatbelt was replaced with its salmon FSH counterpart. Whereas wrapping is less efficient than threading, it may have facilitated natural experimentation with the composition of the seatbelt during the co-evolution of glycoprotein hormones and their receptors. Migration of the seatbelt latch site to the NH(2)-terminal end of the beta-subunit would have facilitated teFSH assembly by a wraparound mechanism and may have contributed also to its ability to distinguish lutropin and follitropin receptors.lld:pubmed
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pubmed-article:15161904pubmed:authorpubmed-author:JiangMeiMlld:pubmed
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pubmed-article:15161904pubmed:pagination35449-57lld:pubmed
pubmed-article:15161904pubmed:dateRevised2007-11-14lld:pubmed
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pubmed-article:15161904pubmed:year2004lld:pubmed
pubmed-article:15161904pubmed:articleTitleGlycoprotein hormone assembly in the endoplasmic reticulum: III. The seatbelt and its latch site determine the assembly pathway.lld:pubmed
pubmed-article:15161904pubmed:affiliationDepartment of Obstetrics and Gynecology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson (Rutgers) Medical School, Piscataway, New Jersey 08854, USA.lld:pubmed
pubmed-article:15161904pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:15161904pubmed:publicationTypeResearch Support, U.S. Gov't, P.H.S.lld:pubmed