Linked Life Data

15166248

Source:http://linkedlifedata.com/resource/pubmed/id/15166248

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
34
pubmed:dateCreated
2004-8-16
pubmed:abstractText
The unique structures of human choriogonadotropin (hCG) and related glycoprotein hormones make them well suited for studies of protein folding in the endoplasmic reticulum. hCG is stabilized by a strand of its beta-subunit that has been likened to a "seatbelt" because it surrounds alpha-subunit loop 2 and its end is "latched" by an intrasubunit disulfide bond to the beta-subunit core. As shown here, assembly begins when parts of the NH(2) terminus, cysteine knot, and loops 1 and 3 of the alpha-subunit dock reversibly with parts of the NH(2) terminus, cystine knot, and loop 2 of the hCG beta-subunit. Whereas the seatbelt can contribute to the stability of the docked subunit complex, it interferes with docking and/or destabilizes the docked complex when it is unlatched. This explains why most hCG is assembled by threading the glycosylated end of alpha-subunit loop 2 beneath the latched seatbelt rather than by wrapping the unlatched seatbelt around this loop. hCG assembly appears to be limited by the need to disrupt the disulfide that stabilizes the small seatbelt loop prior to threading. We postulate that assembly depends on a "zipper-like" sequential formation of intersubunit and intrasubunit hydrogen bonds between backbone atoms of several residues in the beta-subunit cystine knot, alpha-subunit loop 2, and the small seatbelt loop. The resulting intersubunit beta-sheet enhances the stability of the seatbelt loop disulfide, which shortens the seatbelt and secures the heterodimer. Formation of this disulfide also explains the ability of the seatbelt loop to facilitate latching during assembly by the wraparound pathway.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
35458-68
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:15166248-Amino Acid Sequence, pubmed-meshheading:15166248-Animals, pubmed-meshheading:15166248-Binding Sites, pubmed-meshheading:15166248-Chorionic Gonadotropin, pubmed-meshheading:15166248-Chorionic Gonadotropin, beta Subunit, Human, pubmed-meshheading:15166248-Dimerization, pubmed-meshheading:15166248-Disulfides, pubmed-meshheading:15166248-Endoplasmic Reticulum, pubmed-meshheading:15166248-Follicle Stimulating Hormone, pubmed-meshheading:15166248-Glycoprotein Hormones, alpha Subunit, pubmed-meshheading:15166248-Humans, pubmed-meshheading:15166248-Models, Molecular, pubmed-meshheading:15166248-Molecular Sequence Data, pubmed-meshheading:15166248-Mutagenesis, Site-Directed, pubmed-meshheading:15166248-Protein Binding, pubmed-meshheading:15166248-Protein Conformation, pubmed-meshheading:15166248-Protein Folding, pubmed-meshheading:15166248-Protein Structure, Secondary
pubmed:year
2004
pubmed:articleTitle
Glycoprotein hormone assembly in the endoplasmic reticulum: IV. Probable mechanism of subunit docking and completion of assembly.
pubmed:affiliation
Department of Obstetrics and Gynecology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson (Rutgers) Medical School, Piscataway, New Jersey 08854, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.