NDLI: pH-dependent stability of neuroserpin is mediated by histidines 119 and 138; Implications for the control of β-sheet A and polymerization

Content Provider	PubMed Central
Author	Didier, Belorgey Peter, Hägglöf Onda, Maki Lomas, David A.
Abstract	Neuroserpin is a member of the serpin superfamily. Point mutations in the neuroserpin gene underlie the autosomal dominant dementia, familial encephalopathy with neuroserpin inclusion bodies. This is characterized by the retention of ordered polymers of neuroserpin within the endoplasmic reticulum of neurons. pH has been shown to affect the propensity of several serpins to form polymers. In particular, low pH favors the formation of polymers of both α1-antitrypsin and antithrombin. We report here opposite effects in neuroserpin, with a striking resistance to polymer formation at acidic pH. Mutation of specific histidine residues showed that this effect is not attributable to the shutter domain histidine as would be predicted by analogy with other serpins. Indeed, mutation of the shutter domain His338 decreased neuroserpin stability but had no effect on the pH dependence of polymerization when compared with the wild-type protein. In contrast, mutation of His119 or His138 reduced the polymerization of neuroserpin at both acidic and neutral pH. These residues are at the lower pole of neuroserpin and provide a novel mechanism to control the opening of β-sheet A and hence polymerization. This mechanism is likely to have evolved to protect neuroserpin from the acidic environment of the secretory granules.
Related Links	http://dx.doi.org/10.1002/pro.299
Ending Page	228
Page Count	9
Starting Page	220
File Format	PDF
ISSN	09618368
e-ISSN	1469896X
Journal	Protein Science : A Publication of the Protein Society
Issue Number	2
Volume Number	19
Language	English
Publisher	Wiley Subscription Services, Inc., A Wiley Company
Publisher Date	2010-02-01
Access Restriction	Open
Rights Holder	Wiley Subscription Services, Inc., A Wiley Company
Subject Keyword	Biochemistry Molecular Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Medicine Molecular Biology Biochemistry

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

pH-dependent stability of neuroserpin is mediated by histidines 119 and 138; implications for the control of beta-sheet A and polymerization.

β-Sheet-dependent Dimerization Is Essential for the Stability of NhaA Na+/H+ Antiporter

Effects of turn residues in directing the formation of the β-sheet and in the stability of the β-sheet

β-Agonist-mediated Relaxation of Airway Smooth Muscle Is Protein Kinase A-dependent*

Inhibition of Proinflammatory RANTES Expression by TGF-β1 Is Mediated by Glycogen Synthase Kinase-3β-dependent β-Catenin Signaling*

Two Independent Histidines, One in Human Prolactin and One in Its Receptor, Are Critical for pH-dependent Receptor Recognition and Activation*

Sequence determinants of thermodynamic stability in a WW domain—An all-β-sheet protein

Thermodynamics and stability of a β-sheet complex: Molecular dynamics simulations on simplified off-lattice protein models

The study of pH-dependent stability shows that TPLH-mediated hydrogen-bonding network is important for the conformation and stability of human gankyrin †

pH-dependent stability of neuroserpin is mediated by histidines 119 and 138; Implications for the control of β-sheet A and polymerization

Similar Documents

pH-dependent stability of neuroserpin is mediated by histidines 119 and 138; implications for the control of beta-sheet A and polymerization.

β-Sheet-dependent Dimerization Is Essential for the Stability of NhaA Na+/H+ Antiporter

Effects of turn residues in directing the formation of the β-sheet and in the stability of the β-sheet

β-Agonist-mediated Relaxation of Airway Smooth Muscle Is Protein Kinase A-dependent*

Inhibition of Proinflammatory RANTES Expression by TGF-β1 Is Mediated by Glycogen Synthase Kinase-3β-dependent β-Catenin Signaling*

Two Independent Histidines, One in Human Prolactin and One in Its Receptor, Are Critical for pH-dependent Receptor Recognition and Activation*

Sequence determinants of thermodynamic stability in a WW domain—An all-β-sheet protein

Thermodynamics and stability of a β-sheet complex: Molecular dynamics simulations on simplified off-lattice protein models

The study of pH-dependent stability shows that TPLH-mediated hydrogen-bonding network is important for the conformation and stability of human gankyrin †

pH-dependent stability of neuroserpin is mediated by histidines 119 and 138; Implications for the control of β-sheet A and polymerization