Mechanistic insights into a heterobifunctional degrader-induced PTPN2/N1 complex.

PTPN2 (protein tyrosine phosphatase non-receptor type 2, or TC-PTP) and PTPN1 are attractive immuno-oncology targets, with the deletion of Ptpn1 and Ptpn2 improving response to immunotherapy in disease models. Targeted protein degradation has emerged as a promising approach to drug challenging targets including phosphatases. We developed potent PTPN2/N1 dual heterobifunctional degraders (Cmpd-1 and Cmpd-2) which facilitate efficient complex assembly with E3 ubiquitin ligase CRL4, and mediate potent PTPN2/N1 degradation in cells and mice.

From disorder comes function: Regulation of small GTPase function by intrinsically disordered lipidated membrane anchor.

The intrinsically disordered, lipid-modified membrane anchor of small GTPases is emerging as a critical modulator of function through its ability to sort lipids in a conformation-dependent manner. We reviewed recent computational and experimental studies that have begun to shed light on the sequence-ensemble-function relationship in this unique class of lipidated intrinsically disordered regions (LIDRs).

Intrinsically Disordered Membrane Anchors of Rheb, RhoA, and DiRas3 Small GTPases: Molecular Dynamics, Membrane Organization, and Interactions.

Protein structure has been well established to play a key role in determining function; however, intrinsically disordered proteins and regions (IDPs and IDRs) defy this paradigm. IDPs and IDRs exist as an ensemble of structures rather than a stable 3D structure yet play essential roles in many cell-signaling processes. Nearly all Ras superfamily GTPases are tethered to membranes by a lipid tail at the end of a flexible IDR.

Group Size: An Active Ingredient of School-Based Language Therapy.

Purpose: This study explored the relation between therapy group size and language outcomes for children receiving school-based language therapy through an implementation science lens.

Method: Data for the current study were gathered as part of the Speech-Language Therapy Experiences in Public Schools study. Participants included 273 English-speaking kindergarten through second-grade children with language impairment receiving business-as-usual therapy on the caseloads of 75 speech-language pathologists.

Intrinsically disordered membrane anchors of Rheb, RhoA and DiRas3 small GTPases: Molecular dynamics, membrane organization, and interactions.

Protein structure has been well established to play a key role in determining function; however, intrinsically disordered proteins and regions (IDPs and IDRs) defy this paradigm. IDPs and IDRs exist as an ensemble of structures rather than a stable 3D structure yet play essential roles in many cell signaling processes. Nearly all Ras Superfamily GTPases are tethered to membranes by a lipid tail at the end of a flexible IDR.