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Allosteric Modulation of Intrinsically Disordered Proteins

  • Ashfaq Ur Rehman
  • Mueed Ur Rahman
  • Taaha Arshad
  • Hai-Feng ChenEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1163)

Abstract

The allosteric property of globular proteins is applauded as their intrinsic ability to regulate distant sites, and this property further plays a critical role in a wide variety of cellular regulatory mechanisms. Recent advancements and studies have revealed the manifestation of allostery in intrinsically disordered proteins or regions as allosteric sites present within or mediated by IDP/IDRs facilitates the signaling interactions for various biological mechanisms which would otherwise be impossible for globular proteins to regulate. This thematic review has highlighted the biological outcomes that can be achieved by the mechanism of allosteric regulation of intrinsically disordered proteins or regions. The similar mechanism has been implemented on Adenovirus 5 early region 1A and tumor apoptosis protein p53 in correspondence with other partners in binary and ternary complexes, which are the subject of the current review. Both these proteins regulate once they bind to their partners, consequently, forming either a binary or a ternary complex. Allosteric regulation by IDPs is currently a subject undergoing intense study, and the ongoing research work will ensure a better understanding of precision and efficiency of cellular regulation by them. Allosteric regulation mechanism can also be researched by intrinsically disordered protein-specific force field.

Keywords

Allosteric regulation IDPs E1A p53 Partners 

Abbreviations

ATM

Ataxia-telangiectasia mutated (gene ATM)

ATR

Ataxia-telangiectasia and Rad3-related (ATR)

CAK

CDK-activating kinase

CBP

CREB-binding protein (CREBBP)

CDC2

Cell division cycle 2 kinase

CDKs

Cyclin-dependent kinases (multiple members)

CHK1

Cell cycle checkpoint kinase 1 (CHEK1)

CHK2

Cell cycle checkpoint kinase 2 (CHEK2)

CK1

Casein kinase 1 (multiple isoforms)

CK2

Casein kinase 2 (multiple isoforms)

CSN

COP9 signalosome (protein complex)

DNA-PK

DNA-dependent protein kinase (PRKDC)

ERK2

p42 mitogen-activated protein kinase (MAPK1)

FACT

Facilitating chromatin-mediated transcription

HIPK2

Homeodomain-interacting protein kinase 2

JNK

Jun N-terminal kinase (MAPK8)

MDM2

Mouse double-minute 2 homologue

P38

p38 mitogen-activated protein kinase (MAPK14)

P300

E1A-binding protein, 300-kDa (EP300)

PCAF

P300/CBP-associated factor

PKC

Protein kinase C (multiple isoforms)

PKR

Double-stranded RNA-dependent protein kinase (PRKR)

PIAS

Protein inhibitor of activated STAT (multiple isoforms)

PIN1

Peptidyl-prolyl-cis-trans isomerase 1

RSK2

Ribosomal S6 kinase 2 (RPS6KA3)

SET9

SET domain-containing protein 9 (SET9)

STK15

Serine/threonine protein kinase 15

TAF II250

TATA-binding protein-associated factor 250-kD (TAF1)

Notes

Acknowledgment

This work was supported by the Center for HPC at Shanghai Jiao Tong University, the National Key Research and Development Program of China (2018YFC0310803 and 2017YFE0103300), the National Natural Science Foundation of China (31770771 and 31620103901), and the Medical Engineering Cross Fund of Shanghai Jiao Tong University (YG2015MS56 and YG2017MS08).

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Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Ashfaq Ur Rehman
    • 1
    • 2
  • Mueed Ur Rahman
    • 1
  • Taaha Arshad
    • 1
  • Hai-Feng Chen
    • 1
    • 3
    Email author
  1. 1.State Key Laboratory of Microbial Metabolism, Department of Bioinformatics and Biostatistics, National Experimental Teaching Center for Life Sciences and Biotechnology, School of Life Sciences and BiotechnologyShanghai Jiao Tong UniversityShanghaiChina
  2. 2.Department of BiochemistryAbdul Wali Khan University MardanMardanPakistan
  3. 3.Shanghai Center for Bioinformation TechnologyShanghaiChina

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