KAI1, a prostate metastasis' suppressor: Prediction of solvated structure and interactions with binding partners; Integrins, cadherins, and cell-surface receptor proteins

Citation
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
Citations number
95
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
MOLECULAR CARCINOGENESIS
ISSN journal
08991987 → ACNP
Volume
32
Issue
3
Year of publication
2001
Pages
139 - 153
Database
ISI
SICI code
0899-1987(200111)32:3<139:KAPMSP>2.0.ZU;2-9
Abstract
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