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Threading analysis suggests that the obese gene product may be a helical cytokine
Author(s) -
Madej Thomas,
Boguski Mark S.,
Bryant Stephen H.
Publication year - 1995
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(95)00977-h
Subject(s) - threading (protein sequence) , gene , mutant , biology , receptor , protein structure , gene product , genetics , cytokine , peptide sequence , computational biology , gene expression , biochemistry
The ob gene encodes a protein that, in mutant form, is associated with obesity and type II diabetes in mice. Sequence analysis has revealed no similarities to other proteins, however, and no clues as to possible functions. The possibility nonetheless remains that ob is functionally or ancestrally related to other proteins, whose sequences are divergent to the point that only a comparison of three‐dimensional structures might detect relationship. To explore this possibility, we conduct a ‘threading’ search of a 3‐dimensional structure database, to determine whether the ob protein might adopt a fold similar to any known structure. This search reveals that the ob sequence is compatible, at a significance level of P < 0.05, with structures from the family of helical cytokines that includes interleukin‐2 and growth hormone. A structural model of ob based upon these results is physically and biologically plausible and leads to testable predictions, including the prediction that ob may activate the JAK‐STAT pathway, via binding to a receptor resembling those of the cytokine family.