Publication:
Membrane-associated Ras dimers are isoform-specific: K-Ras dimers differ from H-Ras dimers

Placeholder

School / College / Institute

Organizational Unit

Program

KU Authors

Co-Authors

Nussinov, Ruth
Jang, Hyunbum

Publication Date

Language

Embargo Status

Journal Title

Journal ISSN

Volume Title

Alternative Title

Abstract

Are the dimer structures of active Ras isoforms similar? This question is significant since Ras can activate its effectors as a monomer; however, as a dimer, it promotes Raf's activation and MAPK (mitogen-activated protein kinase) cell signalling. In the present study, we model possible catalytic domain dimer interfaces of membrane-anchored GTP-bound K-Ras4B and H-Ras, and compare their conformations. The active helical dimers formed by the allosteric lobe are isoform-specific: K-Ras4B-GTP favours the alpha 3 and alpha 4 interface; H-Ras-GTP favours alpha 4 and alpha 5. Both isoforms also populate a stable beta-sheet dimer interface formed by the effector lobe; a less stable beta-sandwich interface is sustained by salt bridges of the beta-sheet side chains. Raf's high-affinity beta-sheet interaction is promoted by the active helical interface. Collectively, Ras isoforms' dimer conformations are not uniform; instead, the isoform-specific dimers reflect the favoured interactions of the HVRs (hypervariable regions) with cell membrane microdomains, biasing the effector-binding site orientations, thus isoform binding selectivity.

Source

Publisher

Portland Press Ltd

Subject

Biochemistry, Molecular biology

Citation

Has Part

Source

Biochemical Journal

Book Series Title

Edition

DOI

10.1042/BCJ20160031

item.page.datauri

Link

Rights

Copyrights Note

Endorsement

Review

Supplemented By

Referenced By

0

Views

0

Downloads

View PlumX Details