KAI1, a prostate metastasis' suppressor: Prediction of solvated structure and interactions with binding partners; Integrins, cadherins, and cell-surface receptor proteins
Rj. Bienstock et Jc. Barrett, KAI1, a prostate metastasis' suppressor: Prediction of solvated structure and interactions with binding partners; Integrins, cadherins, and cell-surface receptor proteins, MOL CARCINO, 32(3), 2001, pp. 139-153
the solution structure of the transmembrane-4 superfamily protein KAI1, a r
ecently identified prostate cancer metastasis suppressor gene that encodes
a 267-amino acid protein, was modeled. The structure of this four-helical t
ransmembrane protein was developed by defining and modeling sections indivi
dually. A complete three-dimensional structure for the solvated protein was
developed by combining the Individually modeled sections. The four-helix t
ransmembrane bundle structure was predicted combining information from seve
ral methods including Fourier transform analysis of residue variability for
helix orientation. The structure of the KAI1 large extracellular domain wa
s modeled based on the solved crystal structure of the extracellular domain
of another tetraspanin superfamily protein member, CD81 (hepatitis C virus
envelope E2 glycoprotein receptor). This is a novel protein fold consistin
g of five alpha helices held together by two disulfide bonds for which the
CD81 protein is the first solved representative. Molecular dynamics studies
were performed to test stability and to relax the total model KAI1 structu
re's solution. The resulting KAI1 structural model should be a useful tool
for predicting modes of self-association and associations with other TM4SF
proteins, integrins, cadherins, and other KAI1 binding partners. Mutations
for probing the interactions of KAI1 with antibodies and with other binding
partners are suggested. Published 2001 Wiley-Liss, Inc.dagger