Home LiteratureArticle Details
PMID: 18417472 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Structure of the integrin alphaIIb transmembrane segment.

The Journal of biological chemistry ·Vol. 283 ·No. 23 ·2008-06-06 ·Pages 16162-8

Lau TL, Dua V, Ulmer TS

Abstract

Integrin cell-adhesion receptors transduce signals bidirectionally across the plasma membrane via the single-pass transmembrane segments of each alpha and beta subunit. While the beta3 transmembrane segment consists of a linear 29-residue alpha-helix, the structure of the alphaIIb transmembrane segment reveals a linear 24-residue alpha-helix (Ile-966 -Lys-989) followed by a backbone reversal that packs Phe-992-Phe-993 against the transmembrane helix. The length of the alphaIIb transmembrane helix implies the absence of a significant transmembrane helix tilt in contrast to its partnering beta3 subunit. Sequence alignment shows Gly-991-Phe-993 to be fully conserved among all 18 human integrin alpha subunits, suggesting that their unusual structural motif is prototypical for integrin alpha subunits. The alphaIIb transmembrane structure demonstrates a level of complexity within the membrane that is beyond simple transmembrane helices and forms the structural basis for assessing the extent of structural and topological rearrangements upon alphaIIb-beta3 association, i.e. integrin transmembrane signaling.

MeSH Terms
Amino Acid Motifs/physiology Amino Acid Sequence Cell Membrane/chemistry,metabolism Humans Molecular Sequence Data Platelet Glycoprotein GPIIb-IIIa Complex/chemistry,metabolism Platelet Membrane Glycoprotein IIb/chemistry,metabolism Protein Structure, Tertiary/physiology Protein Subunits/chemistry,metabolism Sequence Alignment Signal Transduction/physiology
Chemicals
Platelet Glycoprotein GPIIb-IIIa Complex Platelet Membrane Glycoprotein IIb Protein Subunits
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Lau Tong-Lay
Department of Biochemistry and Molecular Biology and Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.
Dua Varun
Ulmer Tobias S
References (38)
38 references, click to expand
  1. Disrupting integrin transmembrane domain heterodimerization increases ligand binding affinity, not valency or clustering.
    Proc Natl Acad Sci U S A. 2005 Mar 8;102(10):3679-84 PMID: 15738420
  2. Requirement of alpha and beta subunit transmembrane helix separation for integrin outside-in signaling.
    Blood. 2007 Oct 1;110(7):2475-83 PMID: 17615290
  3. The structure and thermal motion of the B800-850 LH2 complex from Rps.acidophila at 2.0A resolution and 100K: new structural features and functionally relevant motions.
    J Mol Biol. 2003 Mar 7;326(5):1523-38 PMID: 12595263
  4. Amide proton relaxation measurements employing a highly deuterated protein.
    J Magn Reson. 2004 Feb;166(2):190-201 PMID: 14729031
  5. An empirical backbone-backbone hydrogen-bonding potential in proteins and its applications to NMR structure refinement and validation.
    J Am Chem Soc. 2004 Jun 16;126(23):7281-92 PMID: 15186165
  6. Determination of N- and C-terminal borders of the transmembrane domain of integrin subunits.
    J Biol Chem. 2004 May 14;279(20):21200-5 PMID: 15016834
  7. Structure of a fluid dioleoylphosphatidylcholine bilayer determined by joint refinement of x-ray and neutron diffraction data. III. Complete structure.
    Biophys J. 1992 Feb;61(2):434-47 PMID: 1547331
  8. NMRPipe: a multidimensional spectral processing system based on UNIX pipes.
    J Biomol NMR. 1995 Nov;6(3):277-93 PMID: 8520220
  9. Integrins: bidirectional, allosteric signaling machines.
    Cell. 2002 Sep 20;110(6):673-87 PMID: 12297042
  10. Structural characterization of proteins with an attached ATCUN motif by paramagnetic relaxation enhancement NMR spectroscopy.
    J Am Chem Soc. 2001 Oct 10;123(40):9843-7 PMID: 11583547
  11. A push-pull mechanism for regulating integrin function.
    Proc Natl Acad Sci U S A. 2005 Feb 1;102(5):1424-9 PMID: 15671157
  12. Measurement of one-bond 15N-13C' dipolar couplings in medium sized proteins.
    J Biomol NMR. 2000 Oct;18(2):101-5 PMID: 11101214
  13. The Xplor-NIH NMR molecular structure determination package.
    J Magn Reson. 2003 Jan;160(1):65-73 PMID: 12565051
  14. Sources of and solutions to problems in the refinement of protein NMR structures against torsion angle potentials of mean force.
    J Magn Reson. 2000 Oct;146(2):249-54 PMID: 11001840
  15. Protein backbone angle restraints from searching a database for chemical shift and sequence homology.
    J Biomol NMR. 1999 Mar;13(3):289-302 PMID: 10212987
  16. Analysis of side-chain rotamers in transmembrane proteins.
    Biophys J. 2004 Nov;87(5):3460-9 PMID: 15339811
  17. Structure and dynamics of micelle-bound human alpha-synuclein.
    J Biol Chem. 2005 Mar 11;280(10):9595-603 PMID: 15615727
  18. Attenuated T2 relaxation by mutual cancellation of dipole-dipole coupling and chemical shift anisotropy indicates an avenue to NMR structures of very large biological macromolecules in solution.
    Proc Natl Acad Sci U S A. 1997 Nov 11;94(23):12366-71 PMID: 9356455
  19. Determination of the border between the transmembrane and cytoplasmic domains of human integrin subunits.
    J Biol Chem. 1999 Dec 24;274(52):37030-4 PMID: 10601259
  20. Sequence-specific assignment of aromatic resonances of uniformly 13C,15N-labeled proteins by using 13C- and 15N-edited NOESY spectra.
    Angew Chem Int Ed Engl. 2006 Mar 13;45(12):1960-3 PMID: 16506301
  21. A simple apparatus for generating stretched polyacrylamide gels, yielding uniform alignment of proteins and detergent micelles.
    J Biomol NMR. 2001 Dec;21(4):377-82 PMID: 11824758
  22. Chi 1 angle information from a simple two-dimensional NMR experiment that identifies trans 3JNC gamma couplings in isotopically enriched proteins.
    J Biomol NMR. 1997 Apr;9(3):323-8 PMID: 9204558
  23. Reconstitution of membrane proteins into lipid-rich bilayered mixed micelles for NMR studies.
    Biochemistry. 1995 Mar 28;34(12):4030-40 PMID: 7696269
  24. Intrahelical hydrogen bonding of serine, threonine and cysteine residues within alpha-helices and its relevance to membrane-bound proteins.
    J Mol Biol. 1984 May 5;175(1):75-81 PMID: 6427470
  25. A structural mechanism of integrin alpha(IIb)beta(3) "inside-out" activation as regulated by its cytoplasmic face.
    Cell. 2002 Sep 6;110(5):587-97 PMID: 12230976
  26. Experimentally determined hydrophobicity scale for proteins at membrane interfaces.
    Nat Struct Biol. 1996 Oct;3(10):842-8 PMID: 8836100
  27. Evaluation of backbone proton positions and dynamics in a small protein by liquid crystal NMR spectroscopy.
    J Am Chem Soc. 2003 Jul 30;125(30):9179-91 PMID: 15369375
  28. A new look at the lipid composition of the plasma membrane of human blood platelets relative to the GPIIb/IIIa (integrin cxIIβ3) content.
    Platelets. 1996;7(4):195-205 PMID: 21043688
  29. Current applications of bicelles in NMR studies of membrane-associated amphiphiles and proteins.
    Biochemistry. 2006 Jul 18;45(28):8453-65 PMID: 16834319
  30. Transmembrane domain helix packing stabilizes integrin alphaIIbbeta3 in the low affinity state.
    J Biol Chem. 2005 Feb 25;280(8):7294-300 PMID: 15591321
  31. Breaking the integrin hinge. A defined structural constraint regulates integrin signaling.
    J Biol Chem. 1996 Mar 22;271(12):6571-4 PMID: 8636068
  32. Quantitative J correlation methods for the accurate measurement of 13C'-13Calpha dipolar couplings in proteins.
    J Biomol NMR. 2004 Oct;30(2):181-94 PMID: 15666562
  33. Predicting 15N chemical shifts in proteins using the preceding residue-specific individual shielding surfaces from phi, psi i-1, and chi 1 torsion angles.
    J Biomol NMR. 2004 Apr;28(4):327-40 PMID: 14872125
  34. Evaluation of cross-correlation effects and measurement of one-bond couplings in proteins with short transverse relaxation times.
    J Magn Reson. 2000 Mar;143(1):184-96 PMID: 10698659
  35. H(C)CH-COSY and (H)CCH-COSY experiments for 13C-labeled proteins in H2O solution.
    J Magn Reson. 1998 Nov;135(1):185-93 PMID: 9799693
  36. A novel cryoprotection scheme for enhancing the diffraction of crystals of recombinant cytochrome ba3 oxidase from Thermus thermophilus.
    Acta Crystallogr D Biol Crystallogr. 2005 Mar;61(Pt 3):340-3 PMID: 15735345
  37. Structure of the integrin beta3 transmembrane segment in phospholipid bicelles and detergent micelles.
    Biochemistry. 2008 Apr 1;47(13):4008-16 PMID: 18321071
  38. Experimentally observed conformation-dependent geometry and hidden strain in proteins.
    Protein Sci. 1996 Jul;5(7):1406-20 PMID: 8819173
Article Info
Journal
The Journal of biological chemistry
Abbr.
J Biol Chem
ISSN
0021-9258
DOI
10.1074/jbc.M801748200
Published
2008-06-06
Epub
2008-00-16
Pages
16162-8
Language
English
Region
United States
NLM ID
2985121R
PMCID
PMC3259656
Subset
IM
Grants
NHLBI NIH HHS · R01 HL089726 · United States
NHLBI NIH HHS · R01 HL089726-01A1 · United States
External Links
PubMed source DOI: 10.1074/jbc.M801748200 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2