PMID- 28844738
OWN - NLM
STAT- In-Data-Review
LR  - 20171101
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1865
IP  - 11 Pt A
DP  - 2017 Nov
TI  - Thermal sensitivity and flexibility of the Cepsilon3 domains in immunoglobulin E.
PG  - 1336-1347
LID - S1570-9639(17)30185-1 [pii]
LID - 10.1016/j.bbapap.2017.08.005 [doi]
AB  - Immunoglobulin E (IgE) is the antibody that plays a central role in the
      mechanisms of allergic diseases such as asthma. Interactions with its receptors, 
      FcepsilonRI on mast cells and CD23 on B cells, are mediated by the Fc region, a
      dimer of the Cepsilon2, Cepsilon3 and Cepsilon4 domains. A sub-fragment lacking
      the Cepsilon2 domains, Fcepsilon3-4, also binds to both receptors, although
      receptor binding almost exclusively involves the Cepsilon3 domains. This domain
      also contains the N-linked glycosylation site conserved in other isotypes. We
      report here the crystal structures of IgE-Fc and Fcepsilon3-4 at the highest
      resolutions yet determined, 1.75A and 2.0A respectively, revealing unprecedented 
      detail regarding the carbohydrate and its interactions with protein domains.
      Analysis of the crystallographic B-factors of these, together with all earlier
      IgE-Fc and Fcepsilon3-4 structures, shows that the Cepsilon3 domains exhibit the 
      greatest intrinsic flexibility and quaternary structural variation within IgE-Fc.
      Intriguingly, both well-ordered carbohydrate and disordered polypeptide can be
      seen within the same Cepsilon3 domain. A simplified method for comparing the
      quaternary structures of the Cepsilon3 domains in free and receptor-bound IgE-Fc 
      structures is presented, which clearly delineates the FcepsilonRI and CD23 bound 
      states. Importantly, differential scanning fluorimetric analysis of IgE-Fc and
      Fcepsilon3-4 identifies Cepsilon3 as the domain most susceptible to
      thermally-induced unfolding, and responsible for the characteristically low
      melting temperature of IgE.
CI  - Copyright (c) 2017 The Author(s). Published by Elsevier B.V. All rights reserved.
FAU - Dore, Katy A
AU  - Dore KA
AD  - King's College London, Randall Division of Cell and Molecular Biophysics, New
      Hunt's House, London SE1 1UL, United Kingdom; Medical Research Council & Asthma
      UK Centre in Allergic Mechanisms of Asthma, London, United Kingdom.
FAU - Davies, Anna M
AU  - Davies AM
AD  - King's College London, Randall Division of Cell and Molecular Biophysics, New
      Hunt's House, London SE1 1UL, United Kingdom; Medical Research Council & Asthma
      UK Centre in Allergic Mechanisms of Asthma, London, United Kingdom.
FAU - Drinkwater, Nyssa
AU  - Drinkwater N
AD  - King's College London, Randall Division of Cell and Molecular Biophysics, New
      Hunt's House, London SE1 1UL, United Kingdom; Medical Research Council & Asthma
      UK Centre in Allergic Mechanisms of Asthma, London, United Kingdom.
FAU - Beavil, Andrew J
AU  - Beavil AJ
AD  - King's College London, Randall Division of Cell and Molecular Biophysics, New
      Hunt's House, London SE1 1UL, United Kingdom; Medical Research Council & Asthma
      UK Centre in Allergic Mechanisms of Asthma, London, United Kingdom.
FAU - McDonnell, James M
AU  - McDonnell JM
AD  - King's College London, Randall Division of Cell and Molecular Biophysics, New
      Hunt's House, London SE1 1UL, United Kingdom; Medical Research Council & Asthma
      UK Centre in Allergic Mechanisms of Asthma, London, United Kingdom.
FAU - Sutton, Brian J
AU  - Sutton BJ
AD  - King's College London, Randall Division of Cell and Molecular Biophysics, New
      Hunt's House, London SE1 1UL, United Kingdom; Medical Research Council & Asthma
      UK Centre in Allergic Mechanisms of Asthma, London, United Kingdom. Electronic
      address: brian.sutton@kcl.ac.uk.
LA  - eng
PT  - Journal Article
DEP - 20170824
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
PMC - PMC5652521
OTO - NOTNLM
OT  - Antibody
OT  - Differential scanning fluorimetry
OT  - Domain flexibility
OT  - Glycosylation
OT  - Immunoglobulin E
OT  - Thermal unfolding
EDAT- 2017/08/29 06:00
MHDA- 2017/08/29 06:00
CRDT- 2017/08/29 06:00
PHST- 2017/06/16 00:00 [received]
PHST- 2017/07/14 00:00 [revised]
PHST- 2017/08/07 00:00 [accepted]
PHST- 2017/08/29 06:00 [pubmed]
PHST- 2017/08/29 06:00 [medline]
PHST- 2017/08/29 06:00 [entrez]
AID - S1570-9639(17)30185-1 [pii]
AID - 10.1016/j.bbapap.2017.08.005 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2017 Nov;1865(11 Pt A):1336-1347. doi:
      10.1016/j.bbapap.2017.08.005. Epub 2017 Aug 24.