PDCL

Last update 08 May 2025

Basic Info

Synonyms

DKFZp564M1863, PDCL, PHLOP1

+ [4]

Introduction

Functions as a co-chaperone for CCT in the assembly of heterotrimeric G protein complexes, facilitates the assembly of both Gbeta-Ggamma and RGS-Gbeta5 heterodimers. Acts as a negative regulator of heterotrimeric G proteins assembly by trapping the preloaded G beta subunits inside the CCT chaperonin. Acts as a positive regulator of hedgehog signaling and regulates ciliary function.

100 Clinical Results associated with PDCL

100 Translational Medicine associated with PDCL

0 Patents (Medical) associated with PDCL

Literatures (Medical) associated with PDCL

01 Jun 2024·STAR Protocols

Protocol to study CCT-mediated folding of Gβ5 by single-particle cryo-EM

Article

Author: Sass, Mikaila I ; Cottam, Samuel L ; Wang, Shuxin ; Mack, Deirdre ; Shen, Peter S ; Willardson, Barry M

The chaperonin CCT mediates folding of many cytosolic proteins, including G protein β subunits (Gβs). Here, we present a protocol for isolating Gβ₅ bound to CCT and its co-chaperone PhLP1 and determining the CCT-mediated folding trajectory of Gβ₅ using single-particle cryoelectron microscopy (cryo-EM) techniques. We describe steps for purifying CCT-Gβ₅-PhLP1 from human cells, stabilizing the closed CCT conformation, preparing and imaging cryo-EM specimens, and processing data to recover multiple Gβ₅ folding intermediates. This protocol permits visualization of protein folding by CCT. For complete details on the use and execution of this protocol, please refer to Sass et al.¹.

01 Nov 2022·Injury

Biomechanical comparison of tuberosity-based proximal humeral locking plate compared to standard proximal humeral locking plate in varus cantilever bending

Article

Author: McKee, Michael D ; Walker, Robert ; Castaneda, Paulo ; Saunders, Patrick E

PURPOSEIn a prior biomechanical study using a tuberosity-based proximal humeral locking plate (TBP) an improvement in greater tuberosity (GT) fixation strength with the TBP compared to a standard proximal humeral locking plate (PHLP) was demonstrated. The purpose of this study is to compare the TBP to the PHLP with a simulated calcar gap fracture under cyclic varus cantilever forces.METHODSSeven matched pairs of cadaveric humeri were studied and 11A2.3 proximal humerus fractures were created by a 1 cm gap osteotomy at the surgical neck. Matched pairs were randomized for fixation using either a PHLP or a TBP. The proximal articular aspect of the humerus was potted and secured to the base of a load frame. The shaft was subjected to cyclic varus cantilever loading with a roller positioned 8 cm from the osteotomy. Change in vertical displacement of the diaphyseal fragment was monitored and digital images were obtained. Failure was defined as vertical displacement greater than 20 mm. Specimens not exhibiting failure over the course of 10,000 cycles were then loaded to 20 mm of vertical displacement. Reactant forces of the specimens at these displacements were recorded.RESULTSFour/seven TBP specimens and four/seven PHLP specimens survived 10,000 cycles. The average cycles to failure for TBP specimens was 7325 cycles and 5715 cycles for PHLP specimens (p = 0.525). For the specimens that survived 10,000 cycles, the decrease in calcar gap was superior in the TBP specimens (p = 0.018). A similar trend was seen when these specimens were loaded to failure where the percent calcar gap recovery was higher for the TBP at 74.71 ± 10.07% versus 53.22 ± 30.35% for the PHLP (p = 0.072). In specimens that were loaded to failure after survival of 10,000 cycles the average stiffness of the TBP construct was 20.51 N/mm, and 11.74 N/mm for the PHLP construct (p = 0.024).CONCLUSIONIn addition to superior GT fixation shown in a prior study, the TBP construct demonstrates significantly greater stiffness at the neck fracture compared to the PHLP, when loaded to failure. In addition, there was a trend towards less collapse in this calcar gap model.

01 May 2022·The FASEB Journal

Structural Analysis of the Roles of CCT and PhLP1 in G Protein β Subunit Folding and Gβγ Dimer Assembly

Article

Author: Kwon, Yujin

Defects in G protein signaling are implicated in host of disorders and diseases, which makes them high value therapeutic targets. While the function of the different G protein subunits has been well‐characterized, little is known about their folding and assembly into complexes. The previous work from our lab showed that CCT and its co‐chaperone PhLP1 are required for the folding of the Gβ subunits and their assembly into complexes with Gγ subunits into the Gβγ dimer. To understand the molecular mechanism of Gβ folding by CCT and PhLP1, we have captured the PhLP1‐Gβ1‐CCT complex and determined its structure by high resolution cryo‐electron microscopy. The structure shows Gβ1 in an unexpected position, sitting between the two CCT rings and interacting with the N‐ and C‐ termini of several CCT subunits. In this position, Gβ appears to have reached a near‐native β‐propeller fold. This result confirms the importance of the terminal regions of the CCT subunits in binding β‐propeller proteins, as we recently observed with Gβ‐like mLST8 subunit of the mTOR complex (Cuellar et al. 2019 Nature Commun. 10, 2865). The structure also elucidates the role of PhLP1 in Gβ1 folding. The PhLP1 C‐terminal domain binds to the apical domains of the CCT3 and CCT6 subunits, while its N‐terminal domain extends down to interact with Gβ1 between the CCT rings. The structure explains why the PhLP1 N‐terminal domain is essential in triggering the release of Gβ1 from CCT to interact with Gγ. These findings suggest that a mimetic of the interaction between the N‐terminal domain of PhLP1 and Gβ1 could block Gβγ assembly and interfere with G protein signaling in disease states caused by excessive G protein signaling.

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