Functional domain analysis of SOX18 transcription factor using a single-chain variable fragment-based approach

Antibodies are routinely used to study the activity of transcription factors, using various in vitro and in vivo approaches such as electrophoretic mobility shift assay, enzyme-linked immunosorbent assay, genome-wide method analysis coupled with next generation sequencing, or mass spectrometry. More...

Full description

Saved in:
Bibliographic Details
Published inmAbs Vol. 10; no. 4; pp. 596 - 606
Main Authors Fontaine, Frank R, Goodall, Stephen, Prokop, Jeremy W, Howard, Christopher B, Moustaqil, Mehdi, Kumble, Sumukh, Rasicci, Daniel T, Osborne, Geoffrey W, Gambin, Yann, Sierecki, Emma, Jones, Martina L, Zuegg, Johannes, Mahler, Stephen, Francois, Mathias
Format Journal Article
LanguageEnglish
Published United States Taylor & Francis 19.05.2018
Subjects
Online AccessGet full text

Cover

Loading…
Abstract Antibodies are routinely used to study the activity of transcription factors, using various in vitro and in vivo approaches such as electrophoretic mobility shift assay, enzyme-linked immunosorbent assay, genome-wide method analysis coupled with next generation sequencing, or mass spectrometry. More recently, a new application for antibodies has emerged as crystallisation scaffolds for difficult to crystallise proteins, such as transcription factors. Only in a few rare cases, antibodies have been used to modulate the activity of transcription factors, and there is a real gap in our knowledge on how to efficiently design antibodies to interfere with transcription. The molecular function of transcription factors is underpinned by complex networks of protein-protein interaction and in theory, setting aside intra-cellular delivery challenges, developing antibody-based approaches to modulate transcription factor activity appears a viable option. Here, we demonstrate that antibodies or an antibody single-chain variable region fragments are powerful molecular tools to unravel complex protein-DNA and protein-protein binding mechanisms. In this study, we focus on the molecular mode of action of the transcription factor SOX18, a key modulator of endothelial cell fate during development, as well as an attractive target in certain pathophysiological conditions such as solid cancer metastasis. The engineered antibody we designed inhibits SOX18 transcriptional activity, by interfering specifically with an 8-amino-acid motif in the C-terminal region directly adjacent to α-Helix 3 of SOX18 HMG domain, thereby disrupting protein-protein interaction. This new approach establishes a framework to guide the study of transcription factors interactomes using antibodies as molecular handles.
AbstractList Antibodies are routinely used to study the activity of transcription factors, using various in vitro and in vivo approaches such as electrophoretic mobility shift assay, enzyme-linked immunosorbent assay, genome-wide method analysis coupled with next generation sequencing, or mass spectrometry. More recently, a new application for antibodies has emerged as crystallisation scaffolds for difficult to crystallise proteins, such as transcription factors. Only in a few rare cases, antibodies have been used to modulate the activity of transcription factors, and there is a real gap in our knowledge on how to efficiently design antibodies to interfere with transcription. The molecular function of transcription factors is underpinned by complex networks of protein-protein interaction and in theory, setting aside intra-cellular delivery challenges, developing antibody-based approaches to modulate transcription factor activity appears a viable option. Here, we demonstrate that antibodies or an antibody single-chain variable region fragments are powerful molecular tools to unravel complex protein-DNA and protein-protein binding mechanisms. In this study, we focus on the molecular mode of action of the transcription factor SOX18, a key modulator of endothelial cell fate during development, as well as an attractive target in certain pathophysiological conditions such as solid cancer metastasis. The engineered antibody we designed inhibits SOX18 transcriptional activity, by interfering specifically with an 8-amino-acid motif in the C-terminal region directly adjacent to α-Helix 3 of SOX18 HMG domain, thereby disrupting protein-protein interaction. This new approach establishes a framework to guide the study of transcription factors interactomes using antibodies as molecular handles.
Antibodies are routinely used to study the activity of transcription factors, using various in vitro and in vivo approaches such as electrophoretic mobility shift assay, enzyme-linked immunosorbent assay, genome-wide method analysis coupled with next generation sequencing, or mass spectrometry. More recently, a new application for antibodies has emerged as crystallisation scaffolds for difficult to crystallise proteins, such as transcription factors. Only in a few rare cases, antibodies have been used to modulate the activity of transcription factors, and there is a real gap in our knowledge on how to efficiently design antibodies to interfere with transcription. The molecular function of transcription factors is underpinned by complex networks of protein-protein interaction and in theory, setting aside intra-cellular delivery challenges, developing antibody-based approaches to modulate transcription factor activity appears a viable option. Here, we demonstrate that antibodies or an antibody single-chain variable region fragments are powerful molecular tools to unravel complex protein-DNA and protein-protein binding mechanisms. In this study, we focus on the molecular mode of action of the transcription factor SOX18, a key modulator of endothelial cell fate during development, as well as an attractive target in certain pathophysiological conditions such as solid cancer metastasis. The engineered antibody we designed inhibits SOX18 transcriptional activity, by interfering specifically with an 8-amino-acid motif in the C-terminal region directly adjacent to α-Helix 3 of SOX18 HMG domain, thereby disrupting protein-protein interaction. This new approach establishes a framework to guide the study of transcription factors interactomes using antibodies as molecular handles.
Author Zuegg, Johannes
Rasicci, Daniel T
Sierecki, Emma
Francois, Mathias
Howard, Christopher B
Fontaine, Frank R
Mahler, Stephen
Moustaqil, Mehdi
Osborne, Geoffrey W
Goodall, Stephen
Prokop, Jeremy W
Jones, Martina L
Kumble, Sumukh
Gambin, Yann
Author_xml – sequence: 1
  givenname: Frank R
  orcidid: 0000-0002-3133-8093
  surname: Fontaine
  fullname: Fontaine, Frank R
  organization: a Institute for Molecular Bioscience, The University of Queensland , Brisbane , Australia
– sequence: 2
  givenname: Stephen
  surname: Goodall
  fullname: Goodall, Stephen
  organization: b Australian Institute for Bioengineering and Nanotechnology, The University of Queensland , QLD , Australia
– sequence: 3
  givenname: Jeremy W
  surname: Prokop
  fullname: Prokop, Jeremy W
  organization: d Department of Pediatrics and Human Development , Michigan State University , East Lansing , MI , USA
– sequence: 4
  givenname: Christopher B
  surname: Howard
  fullname: Howard, Christopher B
  organization: e ARC Training Centre for Biopharmaceutical Innovation, Australian Institute for Bioengineering and Nanotechnology, The University of Queensland , St Lucia , QLD , Australia
– sequence: 5
  givenname: Mehdi
  surname: Moustaqil
  fullname: Moustaqil, Mehdi
  organization: f Single Molecule Science, Lowy Cancer Research Centre, The University of New South Wales , Sydney , NSW , Australia
– sequence: 6
  givenname: Sumukh
  surname: Kumble
  fullname: Kumble, Sumukh
  organization: e ARC Training Centre for Biopharmaceutical Innovation, Australian Institute for Bioengineering and Nanotechnology, The University of Queensland , St Lucia , QLD , Australia
– sequence: 7
  givenname: Daniel T
  surname: Rasicci
  fullname: Rasicci, Daniel T
  organization: c HudsonAlpha Institute for Biotechnology , Huntsville AL , USA
– sequence: 8
  givenname: Geoffrey W
  surname: Osborne
  fullname: Osborne, Geoffrey W
  organization: e ARC Training Centre for Biopharmaceutical Innovation, Australian Institute for Bioengineering and Nanotechnology, The University of Queensland , St Lucia , QLD , Australia
– sequence: 9
  givenname: Yann
  surname: Gambin
  fullname: Gambin, Yann
  organization: f Single Molecule Science, Lowy Cancer Research Centre, The University of New South Wales , Sydney , NSW , Australia
– sequence: 10
  givenname: Emma
  surname: Sierecki
  fullname: Sierecki, Emma
  organization: f Single Molecule Science, Lowy Cancer Research Centre, The University of New South Wales , Sydney , NSW , Australia
– sequence: 11
  givenname: Martina L
  surname: Jones
  fullname: Jones, Martina L
  organization: e ARC Training Centre for Biopharmaceutical Innovation, Australian Institute for Bioengineering and Nanotechnology, The University of Queensland , St Lucia , QLD , Australia
– sequence: 12
  givenname: Johannes
  surname: Zuegg
  fullname: Zuegg, Johannes
  organization: a Institute for Molecular Bioscience, The University of Queensland , Brisbane , Australia
– sequence: 13
  givenname: Stephen
  surname: Mahler
  fullname: Mahler, Stephen
  organization: e ARC Training Centre for Biopharmaceutical Innovation, Australian Institute for Bioengineering and Nanotechnology, The University of Queensland , St Lucia , QLD , Australia
– sequence: 14
  givenname: Mathias
  surname: Francois
  fullname: Francois, Mathias
  organization: a Institute for Molecular Bioscience, The University of Queensland , Brisbane , Australia
BackLink https://www.ncbi.nlm.nih.gov/pubmed/29648920$$D View this record in MEDLINE/PubMed
BookMark eNpVkU1r3DAQhkVJaD6an9CiYy_eaGRbli6FEvIFgRySQG9irJV2VWzJlezA_vvYZLM0uswgve87I54zchRisIR8B7YCJtklqIozKfiKM5ArqGrgUn4hp8t9wWTDjg694CfkIue_bDkNg4Z9JSdciUoqzk5JuJmCGX0M2NF17NEHinO_yz7T6OjT4x-QdEwYskl-WITUoRljolP2YUORLqWzhdku3ldMHtvOUpdw09swFi1mu6Y4DCmi2X4jxw67bC_29Zy83Fw_X90VD4-391e_HwpTAYyFQOmsqCunlJBrW1pe8RawbSU2okEHYIQrEYwqrUIENX-sEq1rZjFAyctz8us9d5ja3q7NvEnCTg_J95h2OqLXn1-C3-pNfNW1ario2Bzwcx-Q4r_J5lH3PhvbdRhsnLLmjNclMFHDLK3fpSbFnJN1hzHA9IJLf-DSCy69xzX7fvy_48H1Aad8A8YSlDY
CitedBy_id crossref_primary_10_3390_genes14010222
crossref_primary_10_1021_acssensors_0c01510
crossref_primary_10_1080_17425247_2020_1781088
crossref_primary_10_1016_j_drudis_2020_02_009
crossref_primary_10_3390_ijms21072301
crossref_primary_10_3390_ijms241411316
Cites_doi 10.1177/1087057104265995
10.1126/science.1058040
10.1038/nbt.1556
10.1098/rsfs.2013.0018
10.1073/pnas.95.11.6157
10.1016/S1359-6446(99)01340-9
10.1016/j.biocel.2009.09.020
10.1182/blood-2013-04-495432
10.1038/nature13182
10.1016/S0021-9258(18)31629-6
10.1038/nature07391
10.1038/nrc906
10.1021/cb100432x
10.1186/2045-9769-3-10
10.1242/dev.133900
10.1016/j.jbiotec.2014.12.006
10.1002/ijc.26325
10.1016/0022-2836(91)90498-U
10.1111/j.1365-2249.2011.04427.x
10.1016/j.jim.2010.02.001
10.1038/nrg2538
10.3892/ijo.2014.2698
10.1126/science.1141319
10.1038/nrm3920
10.1034/j.1399-0004.2000.570403.x
10.1007/s13402-013-0151-7
10.1016/j.chembiol.2017.01.003
10.1074/mcp.O115.052209
10.1093/nar/gkw130
10.1093/nar/gku1075
10.1016/j.canlet.2008.11.014
10.1186/1471-2105-13-S2-S3
10.1074/jbc.M308512200
10.1016/j.str.2011.12.011
10.1172/JCI64547
10.1038/nature15518
10.1101/gr.068130.107
10.1016/j.str.2014.06.014
10.1016/j.cell.2010.01.044
10.1002/jctb.2572
10.1016/j.ymeth.2011.06.006
10.1006/dbio.2000.9883
10.1074/mcp.M113.037275
10.1016/S0092-8674(00)81511-1
10.1038/srep10398
10.1093/bioinformatics/bti079
10.1093/bioinformatics/bti781
10.1093/molbev/msm092
10.1093/nar/gks153
10.1038/nature12294
10.1002/jctb.4545
10.1093/jnci/djj299
10.7554/eLife.21221
10.1038/nbt1126
10.1038/nsmb.1938
ContentType Journal Article
Copyright 2018 Crown Copyright 2018 Crown Copyright
Copyright_xml – notice: 2018 Crown Copyright 2018 Crown Copyright
DBID CGR
CUY
CVF
ECM
EIF
NPM
AAYXX
CITATION
7X8
5PM
DOI 10.1080/19420862.2018.1451288
DatabaseName Medline
MEDLINE
MEDLINE (Ovid)
MEDLINE
MEDLINE
PubMed
CrossRef
MEDLINE - Academic
PubMed Central (Full Participant titles)
DatabaseTitle MEDLINE
Medline Complete
MEDLINE with Full Text
PubMed
MEDLINE (Ovid)
CrossRef
MEDLINE - Academic
DatabaseTitleList MEDLINE

Database_xml – sequence: 1
  dbid: NPM
  name: PubMed
  url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
– sequence: 2
  dbid: EIF
  name: MEDLINE
  url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search
  sourceTypes: Index Database
DeliveryMethod fulltext_linktorsrc
Discipline Pharmacy, Therapeutics, & Pharmacology
DocumentTitleAlternate F. R. FONTAINE ET AL
EISSN 1942-0870
EndPage 606
ExternalDocumentID 10_1080_19420862_2018_1451288
29648920
Genre Research Support, Non-U.S. Gov't
Journal Article
Research Support, N.I.H., Extramural
GrantInformation_xml – fundername: NIEHS NIH HHS
  grantid: K01 ES025435
– fundername: ;
  grantid: APP1048242
– fundername: ;
  grantid: APP1111169
– fundername: ;
  grantid: APP1107643
– fundername: ;
  grantid: DP140100485
GroupedDBID ---
00X
0YH
4.4
53G
ABCCY
ABFIM
ABPEM
ACGFS
ACTIO
ADBBV
ADCVX
AEGYZ
AEISY
AENEX
AIJEM
ALMA_UNASSIGNED_HOLDINGS
AOIJS
AQRUH
BABNJ
BAWUL
BLEHA
C1A
CCCUG
CGR
CUY
CVF
DGEBU
DIK
DKSSO
E3Z
EBS
ECM
EIF
EJD
EMOBN
F5P
GROUPED_DOAJ
H13
HYE
KTTOD
KYCEM
LJTGL
M4Z
NPM
O9-
OK1
OVD
RPM
SV3
TDBHL
TEORI
TFL
TFT
TFW
TR2
TTHFI
AAYXX
CITATION
7X8
5PM
ID FETCH-LOGICAL-c411t-6a8fe654f9968de3e242b1abb8a767af11c6f3a1c93e9aa1970146bf78de11323
IEDL.DBID RPM
ISSN 1942-0862
IngestDate Tue Sep 17 21:28:56 EDT 2024
Wed Dec 04 06:17:52 EST 2024
Fri Dec 06 03:26:44 EST 2024
Sat Sep 28 08:38:07 EDT 2024
IsDoiOpenAccess true
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Issue 4
Keywords protein-protein interaction
antibody
SOX18 transcription factor
scFv
transcriptional activation
Language English
License This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-c411t-6a8fe654f9968de3e242b1abb8a767af11c6f3a1c93e9aa1970146bf78de11323
Notes ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Authors contributed equally to this work.
Supplemental data for this article can be accessed on the publisher's website.
Author to whom correspondence should be directed.
ORCID 0000-0002-3133-8093
OpenAccessLink https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5972640/
PMID 29648920
PQID 2025310651
PQPubID 23479
PageCount 11
ParticipantIDs pubmedcentral_primary_oai_pubmedcentral_nih_gov_5972640
proquest_miscellaneous_2025310651
crossref_primary_10_1080_19420862_2018_1451288
pubmed_primary_29648920
PublicationCentury 2000
PublicationDate 2018-05-19
PublicationDateYYYYMMDD 2018-05-19
PublicationDate_xml – month: 05
  year: 2018
  text: 2018-05-19
  day: 19
PublicationDecade 2010
PublicationPlace United States
PublicationPlace_xml – name: United States
PublicationTitle mAbs
PublicationTitleAlternate MAbs
PublicationYear 2018
Publisher Taylor & Francis
Publisher_xml – name: Taylor & Francis
References cit0033
cit0034
cit0031
cit0030
Koopman P (cit0002) 2001
cit0039
cit0037
cit0038
cit0035
cit0036
cit0022
cit0023
cit0020
cit0021
Tamura K (cit0046) 1993; 10
cit0028
cit0029
cit0026
cit0027
cit0024
cit0025
cit0011
cit0055
cit0012
cit0056
cit0053
cit0010
cit0054
cit0051
cit0052
cit0050
Muse SV (cit0045) 1994; 11
cit0019
cit0017
cit0018
cit0015
cit0016
cit0013
Prokop JW (cit0043) 2012; 13
cit0057
cit0014
cit0058
cit0044
cit0001
cit0042
cit0040
cit0041
cit0008
cit0009
cit0006
cit0007
Orten DJ (cit0032) 1994; 269
cit0004
cit0048
cit0005
cit0049
cit0003
cit0047
References_xml – ident: cit0056
  doi: 10.1177/1087057104265995
– ident: cit0005
  doi: 10.1126/science.1058040
– ident: cit0037
  doi: 10.1038/nbt.1556
– ident: cit0038
  doi: 10.1098/rsfs.2013.0018
– ident: cit0051
  doi: 10.1073/pnas.95.11.6157
– ident: cit0035
  doi: 10.1016/S1359-6446(99)01340-9
– ident: cit0044
  doi: 10.1016/j.biocel.2009.09.020
– ident: cit0057
  doi: 10.1182/blood-2013-04-495432
– ident: cit0012
  doi: 10.1038/nature13182
– volume: 269
  start-page: 32254
  year: 1994
  ident: cit0032
  publication-title: J Biol Chem.
  doi: 10.1016/S0021-9258(18)31629-6
  contributor:
    fullname: Orten DJ
– ident: cit0001
  doi: 10.1038/nature07391
– ident: cit0014
  doi: 10.1038/nrc906
– ident: cit0026
  doi: 10.1021/cb100432x
– ident: cit0025
  doi: 10.1186/2045-9769-3-10
– ident: cit0004
  doi: 10.1242/dev.133900
– ident: cit0058
  doi: 10.1016/j.jbiotec.2014.12.006
– ident: cit0018
  doi: 10.1002/ijc.26325
– ident: cit0053
  doi: 10.1016/0022-2836(91)90498-U
– ident: cit0030
  doi: 10.1111/j.1365-2249.2011.04427.x
– ident: cit0055
  doi: 10.1016/j.jim.2010.02.001
– ident: cit0009
  doi: 10.1038/nrg2538
– ident: cit0016
  doi: 10.3892/ijo.2014.2698
– ident: cit0031
  doi: 10.1126/science.1141319
– ident: cit0008
  doi: 10.1038/nrm3920
– ident: cit0013
  doi: 10.1034/j.1399-0004.2000.570403.x
– ident: cit0017
  doi: 10.1007/s13402-013-0151-7
– ident: cit0028
  doi: 10.1016/j.chembiol.2017.01.003
– ident: cit0029
  doi: 10.1074/mcp.O115.052209
– ident: cit0024
  doi: 10.1093/nar/gkw130
– ident: cit0049
  doi: 10.1093/nar/gku1075
– ident: cit0020
  doi: 10.1016/j.canlet.2008.11.014
– volume: 13
  start-page: S3
  issue: 2
  year: 2012
  ident: cit0043
  publication-title: BMC bioinformatics.
  doi: 10.1186/1471-2105-13-S2-S3
  contributor:
    fullname: Prokop JW
– volume: 10
  start-page: 512
  year: 1993
  ident: cit0046
  publication-title: Mol Biol Evol.
  contributor:
    fullname: Tamura K
– ident: cit0034
  doi: 10.1074/jbc.M308512200
– ident: cit0023
  doi: 10.1016/j.str.2011.12.011
– ident: cit0021
  doi: 10.1172/JCI64547
– ident: cit0006
  doi: 10.1038/nature15518
– ident: cit0007
  doi: 10.1101/gr.068130.107
– ident: cit0042
  doi: 10.1016/j.str.2014.06.014
– ident: cit0011
  doi: 10.1016/j.cell.2010.01.044
– ident: cit0054
  doi: 10.1002/jctb.2572
– volume: 11
  start-page: 715
  year: 1994
  ident: cit0045
  publication-title: Mol Biol Evol.
  contributor:
    fullname: Muse SV
– ident: cit0036
  doi: 10.1016/j.ymeth.2011.06.006
– ident: cit0033
  doi: 10.1006/dbio.2000.9883
– ident: cit0039
  doi: 10.1074/mcp.M113.037275
– ident: cit0003
  doi: 10.1016/S0092-8674(00)81511-1
– ident: cit0040
  doi: 10.1038/srep10398
– ident: cit0047
  doi: 10.1093/bioinformatics/bti079
– start-page: 25
  issue: 91
  year: 2001
  ident: cit0002
  publication-title: EXS.
  contributor:
    fullname: Koopman P
– ident: cit0015
  doi: 10.1093/bioinformatics/bti781
– ident: cit0048
  doi: 10.1093/molbev/msm092
– ident: cit0050
  doi: 10.1093/nar/gks153
– ident: cit0010
  doi: 10.1038/nature12294
– ident: cit0041
  doi: 10.1002/jctb.4545
– ident: cit0019
  doi: 10.1093/jnci/djj299
– ident: cit0027
  doi: 10.7554/eLife.21221
– ident: cit0052
  doi: 10.1038/nbt1126
– ident: cit0022
  doi: 10.1038/nsmb.1938
SSID ssj0000070170
Score 2.2523422
Snippet Antibodies are routinely used to study the activity of transcription factors, using various in vitro and in vivo approaches such as electrophoretic mobility...
Antibodies are routinely used to study the activity of transcription factors, using various in vitro and in vivo approaches such as electrophoretic mobility...
SourceID pubmedcentral
proquest
crossref
pubmed
SourceType Open Access Repository
Aggregation Database
Index Database
StartPage 596
SubjectTerms Humans
Single-Chain Antibodies
SOXF Transcription Factors - analysis
SOXF Transcription Factors - chemistry
Title Functional domain analysis of SOX18 transcription factor using a single-chain variable fragment-based approach
URI https://www.ncbi.nlm.nih.gov/pubmed/29648920
https://search.proquest.com/docview/2025310651
https://pubmed.ncbi.nlm.nih.gov/PMC5972640
Volume 10
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1LT9wwEB6xnLigPqBsH8iVECe8G-dl-1ihrlaVKCsB0vYU2Y4NK7FZBEsl_n1nkhjY9tZTJGccORnH34w98w3AUamtCsGikyMLyXNc8bgpvOFSeHSIdKrqtn7K2c9yepX_mBfzLShiLkwbtO_sYtTcLkfN4qaNrbxbunGMExvPzk7RCEYcT8YDGCD8vnLRO5tXEidMe5qcp5xM9pi5o5IxtVETBXWpEZWpTRXV7KPTRxxasglP_9icf4dOvsKiyRvY7Y1I9q0b7FvY8s07OJ51LNRPJ-zyJanq4YQds9kLP_XTe2gmiGXdFiCrV0uzaJjpqUnYKrCL87lQbE0YFlcU1lXlYRQkf80Mo8ut5-6G-v5Gb5vyr1i4N9e018gJGWsW2cr34Gry_fJ0yvuyC9zlQqx5aVTwZZEHdIVU7TOPKG6FsVYZWUoThHBlyIxwOvPaGKElEdDYIFGY6tZn-7DdrBp_AKwUpra5dU77JM-d1i4RJhQ2LdGR8SEbwih-7equY9eoRE9aGjVVkaaqXlND-Bp1UuF_QIcbpvGrxweUSnE5QYNKDOFDp6PnR0blDkFuaO9ZgDi2N-_g1Gu5tvup9vG_e36CHXoBCjgQ-jNsr-8f_Re0Y9b2EAbJr-lhO3v_AF1P8jk
link.rule.ids 230,314,727,780,784,885,27924,27925,53791,53793
linkProvider National Library of Medicine
linkToHtml http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Lb9swDCa67rBdhr2bPTVg6KlKLL8kHYdiQbY1XYClQG6GJEttgMYp2nRA__1I22qb7baTAZkyZFPWR0rkR4DPpbYqBItOjiwkz3HF46bwhkvh0SHSqarb-inT43Jykn9fFIsdKGIuTBu07-xy2Jyvhs3yrI2tvFi5UYwTG82mh2gEI44nowfwsMikFvec9M7qlcQK054n5yknoz3m7qhkRG3URGFdakiFalNFVfvo_BEHl2wD1D9W59_Bk_fQaPwUnvRmJPvSDfcZ7PjmOezPOh7qmwM2v0urujpg-2x2x1B98wKaMaJZtwnI6vXKLBtmenIStg7s18-FUGxDKBbXFNbV5WEUJn_KDKPLuefujPr-Rn-bMrBYuDSntNvICRtrFvnKX8LJ-Ov8cML7wgvc5UJseGlU8GWRB3SGVO0zjzhuhbFWGVlKE4RwZciMcDrz2hihJVHQ2CBRmCrXZ69gt1k3fg9YKUxtc-uc9kmeO61dIkwobFqiK-NDNoBh_NrVRcevUYmetjRqqiJNVb2mBvAp6qTCP4GON0zj19dXKJXigoImlRjA605Ht4-Myh2A3NLerQCxbG_fwcnXsm33k-3Nf_f8CI8m8-lRdfTt-MdbeEwvQ-EHQr-D3c3ltX-PVs3Gfmjn8B-MC_Sc
linkToPdf http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1LT9wwEB5RkKpeqpa-ti9cqeKEN3Feto8V7QpooSsVpL1FtmPDSmx2BUsl_n1n8oDdcuMUyRlHTmbib8YefwPwtdBWhWAxyJG55BnOeNzk3nApPAZEOlFVUz_l-KQ4OMuOJvlkpdRXk7Tv7HRYX86G9fSiya1czFzU54lF4-N9dIIRx-NoUYXoCWzlKRrZSqDeer6SmGGaPeUs4eS49-d3VBxRGzVRapcaUrHaRFHlPtqDxAHG6yD1wPP8P4FyBZFGL-B550qyb-2QX8KGr7dhd9xyUd_usdP7o1XXe2yXje9Zqm9fQT1CRGsXAlk1n5lpzUxHUMLmgf35PRGKLQnJ-nmFtbV5GKXKnzPD6HLpubugvn8x5qZTWCxcmXNaceSEjxXrOctfw9nox-n-Ae-KL3CXCbHkhVHBF3kWMCBSlU89YrkVxlplZCFNEMIVITXC6dRrY4SWRENjg0Rhql6fvoHNel77d8AKYSqbWee0j7PMae1iYUJukwLDGR_SAQz7r10uWo6NUnTUpb2mStJU2WlqAF96nZT4N9AWh6n9_OYapRKcVNCtEgN42-ro7pG9cgcg17R3J0BM2-t30AAbxu3O4N4_uucOPB1_H5W_Dk9-foBn9C6UgSD0R9hcXt34T-jYLO3nxoT_ARl59a8
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Functional+domain+analysis+of+SOX18+transcription+factor+using+a+single-chain+variable+fragment-based+approach&rft.jtitle=mAbs&rft.au=Fontaine%2C+Frank+R&rft.au=Goodall%2C+Stephen&rft.au=Prokop%2C+Jeremy+W&rft.au=Howard%2C+Christopher+B&rft.date=2018-05-19&rft.eissn=1942-0870&rft.volume=10&rft.issue=4&rft.spage=596&rft.epage=606&rft_id=info:doi/10.1080%2F19420862.2018.1451288&rft.externalDBID=NO_FULL_TEXT
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1942-0862&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1942-0862&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1942-0862&client=summon