STRUCTURAL STUDY OF INTRINSICALLY DISORDERED PROTEIN P130CAS SUBSTRATE DOMAIN

Abstract

THE MAIN FOCUS OF THIS STUDY IS THE STRUCTURAL STUDY OF A LARGE INTRINSICALLY DISORDERED PROTEIN P130CASSD, WHICH IS AN IMPORTANT SUBSTRATE FOR TYROSINE PHOSPHORYLATION. IN VITRO EXPERIMENTS OF EXTENSION AND PHOSPHORYLATION OF P130CASSD SUGGESTED THAT CAS PLAYS A ROLE AS A PRIMARY FORCE SENSOR, TRANSDUCING FORCE INTO EXTENSION-DEPENDENT PHOSPHORYLATION, THUS TRIGGERING OFF DOWNSTREAM SIGNALING. A SERIES OF NMR EXPERIMENTS HAVE BEEN PERFORMED TO CHARACTERIZE THE STRUCTURE AND DYNAMICS OF P130CASSD. IN ORDER TO OBTAIN RESONANCE ASSIGNMENTS OF P130CASSD WITH 306 AMINO ACIDS INCLUDING 64 PROLINE RESIDUES, 3D HN(CA)N AND HN(COCA)N EXPERIMENTS WERE DEVELOPED FOR BACKBONE ASSIGNMENT. REFERRING TO THE DESIGN OF A SOFTWARE TOOL XYZ4D, FREE3D+ WAS DEVELOPED TO FACILITATE BACKBONE ASSIGNMENT OF P130CASSD AS AN EXTENSION OF NMRSPY.