Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Structural basis for pleckstrin homology domain mutations in X-linked agammaglobulinemia

Vihinen, Mauno LU orcid ; ZVELEBIL, MJJM ; ZHU, QL ; BROOIMANS, RA ; OCHS, HD ; ZEGERS, BJM ; NILSSON, L ; WATERFIELD, MD and SMITH, CIE (1995) In Biochemistry 34(5). p.1475-1481
Abstract
Deficiencies in a tyrosine kinase, designated Btk, cause X-linked agammaglobulinemia (XLA) in man, a hereditary defect of B-cell differentiation. Mutations in the newly found PH domain located at the N-terminus of Btk have been shown to be the direct cause of XLA, and here two new mutations, T33P and V64F, are presented. Btk is thus far the only protein in which mutations of the PH domain have been found to cause a disease. The three-dimensional structure of the Btk PH domain was modeled on the basis of the dynamin PH structure. Despite a relatively low sequence similarity the Btk PH domain seems to have the same two P-sheet structure observed in the known structures. The model was used to interpret the structural basis for disease in five... (More)
Deficiencies in a tyrosine kinase, designated Btk, cause X-linked agammaglobulinemia (XLA) in man, a hereditary defect of B-cell differentiation. Mutations in the newly found PH domain located at the N-terminus of Btk have been shown to be the direct cause of XLA, and here two new mutations, T33P and V64F, are presented. Btk is thus far the only protein in which mutations of the PH domain have been found to cause a disease. The three-dimensional structure of the Btk PH domain was modeled on the basis of the dynamin PH structure. Despite a relatively low sequence similarity the Btk PH domain seems to have the same two P-sheet structure observed in the known structures. The model was used to interpret the structural basis for disease in five independent point mutations and in an insertion in patients with XLA. The mutated residues F25, V64, and V113, and possibly residue(s) around Q103, could form a binding site, since these amino acids are located close to each other on the surface of the molecule. (Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
subject
in
Biochemistry
volume
34
issue
5
pages
1475 - 1481
publisher
The American Chemical Society (ACS)
external identifiers
  • wos:A1995QF83700002
  • scopus:0028943589
ISSN
0006-2960
DOI
10.1021/bi00005a002
language
English
LU publication?
no
id
b66990c3-e626-4527-aca6-f6b0236b1d6e (old id 3853254)
date added to LUP
2016-04-01 12:36:21
date last changed
2021-01-03 06:04:28
@article{b66990c3-e626-4527-aca6-f6b0236b1d6e,
  abstract     = {{Deficiencies in a tyrosine kinase, designated Btk, cause X-linked agammaglobulinemia (XLA) in man, a hereditary defect of B-cell differentiation. Mutations in the newly found PH domain located at the N-terminus of Btk have been shown to be the direct cause of XLA, and here two new mutations, T33P and V64F, are presented. Btk is thus far the only protein in which mutations of the PH domain have been found to cause a disease. The three-dimensional structure of the Btk PH domain was modeled on the basis of the dynamin PH structure. Despite a relatively low sequence similarity the Btk PH domain seems to have the same two P-sheet structure observed in the known structures. The model was used to interpret the structural basis for disease in five independent point mutations and in an insertion in patients with XLA. The mutated residues F25, V64, and V113, and possibly residue(s) around Q103, could form a binding site, since these amino acids are located close to each other on the surface of the molecule.}},
  author       = {{Vihinen, Mauno and ZVELEBIL, MJJM and ZHU, QL and BROOIMANS, RA and OCHS, HD and ZEGERS, BJM and NILSSON, L and WATERFIELD, MD and SMITH, CIE}},
  issn         = {{0006-2960}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{1475--1481}},
  publisher    = {{The American Chemical Society (ACS)}},
  series       = {{Biochemistry}},
  title        = {{Structural basis for pleckstrin homology domain mutations in X-linked agammaglobulinemia}},
  url          = {{http://dx.doi.org/10.1021/bi00005a002}},
  doi          = {{10.1021/bi00005a002}},
  volume       = {{34}},
  year         = {{1995}},
}