Structure of the PAPP-ABP5 complex reveals mechanism of substrate recognition

PAPP-A substrate selectivity underlies the tight regulation of IGF signaling. Here, the authors report cryo-EM structures of dimeric PAPP-A in its substrate-free form and in complex with a peptide substrate, which combined with biochemical assays provide a mechanism for PAPP-A substrate binding and...

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Main Authors: Russell A. Judge, Janani Sridar, Kathryn Tunyasunvunakool, Rinku Jain, John C. K. Wang, Christna Ouch, Jun Xu, Amirhossein Mafi, Aaron H. Nile, Clint Remarcik, Corey L. Smith, Crystal Ghosh, Chen Xu, Vincent Stoll, John Jumper, Amoolya H. Singh, Dan Eaton, Qi Hao
Format: Article
Language:English
Published: Nature Portfolio 2022-09-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-022-33175-2
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author Russell A. Judge
Janani Sridar
Kathryn Tunyasunvunakool
Rinku Jain
John C. K. Wang
Christna Ouch
Jun Xu
Amirhossein Mafi
Aaron H. Nile
Clint Remarcik
Corey L. Smith
Crystal Ghosh
Chen Xu
Vincent Stoll
John Jumper
Amoolya H. Singh
Dan Eaton
Qi Hao
author_facet Russell A. Judge
Janani Sridar
Kathryn Tunyasunvunakool
Rinku Jain
John C. K. Wang
Christna Ouch
Jun Xu
Amirhossein Mafi
Aaron H. Nile
Clint Remarcik
Corey L. Smith
Crystal Ghosh
Chen Xu
Vincent Stoll
John Jumper
Amoolya H. Singh
Dan Eaton
Qi Hao
author_sort Russell A. Judge
collection DOAJ
description PAPP-A substrate selectivity underlies the tight regulation of IGF signaling. Here, the authors report cryo-EM structures of dimeric PAPP-A in its substrate-free form and in complex with a peptide substrate, which combined with biochemical assays provide a mechanism for PAPP-A substrate binding and selectivity.
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spelling doaj.art-b5c3045813c44acc833427452b1f84342022-12-22T02:05:54ZengNature PortfolioNature Communications2041-17232022-09-0113111310.1038/s41467-022-33175-2Structure of the PAPP-ABP5 complex reveals mechanism of substrate recognitionRussell A. Judge0Janani Sridar1Kathryn Tunyasunvunakool2Rinku Jain3John C. K. Wang4Christna Ouch5Jun Xu6Amirhossein Mafi7Aaron H. Nile8Clint Remarcik9Corey L. Smith10Crystal Ghosh11Chen Xu12Vincent Stoll13John Jumper14Amoolya H. Singh15Dan Eaton16Qi Hao17AbbVieCalico Life Sciences LLCDeepMindAbbVieCalico Life Sciences LLCDepartment of Biochemistry & Molecular Biotechnology, University of Massachusetts Chan Medical SchoolCalico Life Sciences LLCCalico Life Sciences LLCCalico Life Sciences LLCCalico Life Sciences LLCAbbVie Bioresearch CenterCalico Life Sciences LLCDepartment of Biochemistry & Molecular Biotechnology, University of Massachusetts Chan Medical SchoolAbbVieDeepMindCalico Life Sciences LLCCalico Life Sciences LLCCalico Life Sciences LLCPAPP-A substrate selectivity underlies the tight regulation of IGF signaling. Here, the authors report cryo-EM structures of dimeric PAPP-A in its substrate-free form and in complex with a peptide substrate, which combined with biochemical assays provide a mechanism for PAPP-A substrate binding and selectivity.https://doi.org/10.1038/s41467-022-33175-2
spellingShingle Russell A. Judge
Janani Sridar
Kathryn Tunyasunvunakool
Rinku Jain
John C. K. Wang
Christna Ouch
Jun Xu
Amirhossein Mafi
Aaron H. Nile
Clint Remarcik
Corey L. Smith
Crystal Ghosh
Chen Xu
Vincent Stoll
John Jumper
Amoolya H. Singh
Dan Eaton
Qi Hao
Structure of the PAPP-ABP5 complex reveals mechanism of substrate recognition
Nature Communications
title Structure of the PAPP-ABP5 complex reveals mechanism of substrate recognition
title_full Structure of the PAPP-ABP5 complex reveals mechanism of substrate recognition
title_fullStr Structure of the PAPP-ABP5 complex reveals mechanism of substrate recognition
title_full_unstemmed Structure of the PAPP-ABP5 complex reveals mechanism of substrate recognition
title_short Structure of the PAPP-ABP5 complex reveals mechanism of substrate recognition
title_sort structure of the papp abp5 complex reveals mechanism of substrate recognition
url https://doi.org/10.1038/s41467-022-33175-2
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