Progranulin directly binds to the CRD2 and CRD3 of TNFR extracellular domains

Jinlong Jian; Shuai Zhao; Qingyun Tian; Elena Gonzalez-Gugel; Jyoti Joshi Mundra; Sardar Mz Uddin; Ben Liu; Brendon Richbourgh; Ryan Brunetti; Chuan Ju Liu

doi:10.1016/j.febslet.2013.09.024

Progranulin directly binds to the CRD2 and CRD3 of TNFR extracellular domains

Jinlong Jian, Shuai Zhao, Qingyun Tian, Elena Gonzalez-Gugel, Jyoti Joshi Mundra, Sardar Mz Uddin, Ben Liu, Brendon Richbourgh, Ryan Brunetti, Chuan Ju Liu

Research output: Contribution to journal › Article › peer-review

61 Scopus citations

Abstract

Abstract We previously reported that PGRN directly bound to TNF receptors (TNFR) in vitro and in chondrocytes (Tang, et al.; Science, 2011). Here we report that PGRN also associated with TNFR in splenocytes, and inhibited the binding of TNFα to immune cells. Proper folding of PGRN is essential for its binding to TNFR, as DTT treatment abolished its binding to TNFR. In contrast, the binding of PGRN to Sortilin was enhanced by DTT. Protein interaction assays with mutants of the TNFR extracellular domain demonstrated that CRD2 and CRD3 of TNFR are important for the interaction with PGRN, similar to the binding to TNFα. Taken together, these findings provide the molecular basis underlying PGRN/TNFR interaction and PGRN-mediated anti-inflammatory activity in various autoimmune diseases and conditions.

Original language	English
Pages (from-to)	3428-3436
Number of pages	9
Journal	FEBS Letters
Volume	587
Issue number	21
DOIs	https://doi.org/10.1016/j.febslet.2013.09.024
State	Published - 1 Nov 2013
Externally published	Yes

Keywords

PGRN
Protein interaction
Sortilin
TNFR
TNFα

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10.1016/j.febslet.2013.09.024

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@article{b63bafd0fa8f40279ad05c9b2e7fa792,

title = "Progranulin directly binds to the CRD2 and CRD3 of TNFR extracellular domains",

abstract = "Abstract We previously reported that PGRN directly bound to TNF receptors (TNFR) in vitro and in chondrocytes (Tang, et al.; Science, 2011). Here we report that PGRN also associated with TNFR in splenocytes, and inhibited the binding of TNFα to immune cells. Proper folding of PGRN is essential for its binding to TNFR, as DTT treatment abolished its binding to TNFR. In contrast, the binding of PGRN to Sortilin was enhanced by DTT. Protein interaction assays with mutants of the TNFR extracellular domain demonstrated that CRD2 and CRD3 of TNFR are important for the interaction with PGRN, similar to the binding to TNFα. Taken together, these findings provide the molecular basis underlying PGRN/TNFR interaction and PGRN-mediated anti-inflammatory activity in various autoimmune diseases and conditions.",

keywords = "PGRN, Protein interaction, Sortilin, TNFR, TNFα",

author = "Jinlong Jian and Shuai Zhao and Qingyun Tian and Elena Gonzalez-Gugel and Mundra, {Jyoti Joshi} and Uddin, {Sardar Mz} and Ben Liu and Brendon Richbourgh and Ryan Brunetti and Liu, {Chuan Ju}",

note = "Funding Information: We would like to thank the scientists at Atreaon, Inc., a biotechnology company in Newton, MA, for providing us with their SPR data concerning PGRN/TNFR interaction used in this paper. This work was supported partly by NIH research grants R01AR062207, R01AR061484, R56AI100901, and a Disease Targeted Research Grant from Rheumatology Research Foundation. ",

year = "2013",

month = nov,

day = "1",

doi = "10.1016/j.febslet.2013.09.024",

language = "English",

volume = "587",

pages = "3428--3436",

journal = "FEBS Letters",

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publisher = "John Wiley and Sons Inc.",

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TY - JOUR

T1 - Progranulin directly binds to the CRD2 and CRD3 of TNFR extracellular domains

AU - Jian, Jinlong

AU - Zhao, Shuai

AU - Tian, Qingyun

AU - Gonzalez-Gugel, Elena

AU - Mundra, Jyoti Joshi

AU - Uddin, Sardar Mz

AU - Liu, Ben

AU - Richbourgh, Brendon

AU - Brunetti, Ryan

AU - Liu, Chuan Ju

N1 - Funding Information: We would like to thank the scientists at Atreaon, Inc., a biotechnology company in Newton, MA, for providing us with their SPR data concerning PGRN/TNFR interaction used in this paper. This work was supported partly by NIH research grants R01AR062207, R01AR061484, R56AI100901, and a Disease Targeted Research Grant from Rheumatology Research Foundation.

PY - 2013/11/1

Y1 - 2013/11/1

N2 - Abstract We previously reported that PGRN directly bound to TNF receptors (TNFR) in vitro and in chondrocytes (Tang, et al.; Science, 2011). Here we report that PGRN also associated with TNFR in splenocytes, and inhibited the binding of TNFα to immune cells. Proper folding of PGRN is essential for its binding to TNFR, as DTT treatment abolished its binding to TNFR. In contrast, the binding of PGRN to Sortilin was enhanced by DTT. Protein interaction assays with mutants of the TNFR extracellular domain demonstrated that CRD2 and CRD3 of TNFR are important for the interaction with PGRN, similar to the binding to TNFα. Taken together, these findings provide the molecular basis underlying PGRN/TNFR interaction and PGRN-mediated anti-inflammatory activity in various autoimmune diseases and conditions.

AB - Abstract We previously reported that PGRN directly bound to TNF receptors (TNFR) in vitro and in chondrocytes (Tang, et al.; Science, 2011). Here we report that PGRN also associated with TNFR in splenocytes, and inhibited the binding of TNFα to immune cells. Proper folding of PGRN is essential for its binding to TNFR, as DTT treatment abolished its binding to TNFR. In contrast, the binding of PGRN to Sortilin was enhanced by DTT. Protein interaction assays with mutants of the TNFR extracellular domain demonstrated that CRD2 and CRD3 of TNFR are important for the interaction with PGRN, similar to the binding to TNFα. Taken together, these findings provide the molecular basis underlying PGRN/TNFR interaction and PGRN-mediated anti-inflammatory activity in various autoimmune diseases and conditions.

KW - PGRN

KW - Protein interaction

KW - Sortilin

KW - TNFR

KW - TNFα

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U2 - 10.1016/j.febslet.2013.09.024

DO - 10.1016/j.febslet.2013.09.024

M3 - Article

C2 - 24070898

AN - SCOPUS:84886285288

SN - 0014-5793

VL - 587

SP - 3428

EP - 3436

JO - FEBS Letters

JF - FEBS Letters

IS - 21

ER -

Progranulin directly binds to the CRD2 and CRD3 of TNFR extracellular domains

Abstract

Keywords

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