6OM2

Crystal structure of atypical integrin alphaV beta8 with proTGF-beta1 ligand peptide

  • Classification: IMMUNE SYSTEM
  • Organism(s): Homo sapiens
  • Expression System: Homo sapiens
  • Mutation(s): Yes 

  • Deposited: 2019-04-17 Released: 2019-12-11 
  • Deposition Author(s): Wang, J.C., Springer, T.A.
  • Funding Organization(s): National Institutes of Health/National Human Genome Research Institute (NIH/NHGRI)

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.77 Å
  • R-Value Free: 0.282 
  • R-Value Work: 0.251 
  • R-Value Observed: 0.252 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 2.1 of the entry. See complete history


Literature

General structural features that regulate integrin affinity revealed by atypical alpha V beta 8.

Wang, J.Su, Y.Iacob, R.E.Engen, J.R.Springer, T.A.

(2019) Nat Commun 10: 5481-5481

  • DOI: https://doi.org/10.1038/s41467-019-13248-5
  • Primary Citation of Related Structures:  
    6OM1, 6OM2

  • PubMed Abstract: 

    Integrin αVβ8, which like αVβ6 functions to activate TGF-βs, is atypical. Its β8 subunit binds to a distinctive cytoskeleton adaptor and does not exhibit large changes in conformation upon binding to ligand. Here, crystal structures, hydrogen-deuterium exchange dynamics, and affinity measurements on mutants are used to compare αVβ8 and αVβ6. Lack of a binding site for one of three βI domain divalent cations and a unique β6-α7 loop conformation in β8 facilitate movements of the α1 and α1' helices at the ligand binding pocket toward the high affinity state, without coupling to β6-α7 loop reshaping and α7-helix pistoning that drive large changes in βI domain-hybrid domain orientation seen in other integrins. Reciprocal swaps between β6 and β8 βI domains increase affinity of αVβ6 and decrease affinity of αVβ8 and define features that regulate affinity of the βI domain and its coupling to the hybrid domain.


  • Organizational Affiliation

    Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Integrin alpha-V
A, C
598Homo sapiensMutation(s): 1 
Gene Names: ITGAVMSK8VNRAVTNR
UniProt & NIH Common Fund Data Resources
Find proteins for P06756 (Homo sapiens)
Explore P06756 
Go to UniProtKB:  P06756
PHAROS:  P06756
GTEx:  ENSG00000138448 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP06756
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Integrin beta-8
B, D
421Homo sapiensMutation(s): 1 
Gene Names: ITGB8
UniProt & NIH Common Fund Data Resources
Find proteins for P26012 (Homo sapiens)
Explore P26012 
Go to UniProtKB:  P26012
PHAROS:  P26012
GTEx:  ENSG00000105855 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP26012
Sequence Annotations
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  • Reference Sequence

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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
proTGF-beta1 RGD peptide
E, F
11Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P01137 (Homo sapiens)
Explore P01137 
Go to UniProtKB:  P01137
PHAROS:  P01137
GTEx:  ENSG00000105329 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP01137
Sequence Annotations
Expand
  • Reference Sequence
Oligosaccharides

Help

Entity ID: 4
MoleculeChains Length2D Diagram Glycosylation3D Interactions
beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
G, K, S
3N-Glycosylation
Glycosylation Resources
GlyTouCan:  G15407YE
GlyCosmos:  G15407YE
GlyGen:  G15407YE
Entity ID: 5
MoleculeChains Length2D Diagram Glycosylation3D Interactions
alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-3)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
H, L, O
7N-Glycosylation
Glycosylation Resources
GlyTouCan:  G55220VL
GlyCosmos:  G55220VL
GlyGen:  G55220VL
Entity ID: 6
MoleculeChains Length2D Diagram Glycosylation3D Interactions
alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
I
5N-Glycosylation
Glycosylation Resources
GlyTouCan:  G22768VO
GlyCosmos:  G22768VO
GlyGen:  G22768VO
Entity ID: 7
MoleculeChains Length2D Diagram Glycosylation3D Interactions
alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
J
4N-Glycosylation
Glycosylation Resources
GlyTouCan:  G81315DD
GlyCosmos:  G81315DD
GlyGen:  G81315DD
Entity ID: 8
MoleculeChains Length2D Diagram Glycosylation3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
M, P, Q, R
2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G42666HT
GlyCosmos:  G42666HT
GlyGen:  G42666HT
Entity ID: 9
MoleculeChains Length2D Diagram Glycosylation3D Interactions
alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-3)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
N
6N-Glycosylation
Glycosylation Resources
GlyTouCan:  G09724ZC
GlyCosmos:  G09724ZC
GlyGen:  G09724ZC
Small Molecules
Ligands 5 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NAG
Query on NAG

Download Ideal Coordinates CCD File 
IA [auth D],
X [auth A],
Y [auth A]
2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
PEG
Query on PEG

Download Ideal Coordinates CCD File 
HA [auth C],
Z [auth A]
DI(HYDROXYETHYL)ETHER
C4 H10 O3
MTHSVFCYNBDYFN-UHFFFAOYSA-N
GLY
Query on GLY

Download Ideal Coordinates CCD File 
CA [auth C]GLYCINE
C2 H5 N O2
DHMQDGOQFOQNFH-UHFFFAOYSA-N
CA
Query on CA

Download Ideal Coordinates CCD File 
BA [auth B]
DA [auth C]
EA [auth C]
FA [auth C]
GA [auth C]
BA [auth B],
DA [auth C],
EA [auth C],
FA [auth C],
GA [auth C],
JA [auth D],
T [auth A],
U [auth A],
V [auth A],
W [auth A]
CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
MG
Query on MG

Download Ideal Coordinates CCD File 
AA [auth B],
KA [auth D]
MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.77 Å
  • R-Value Free: 0.282 
  • R-Value Work: 0.251 
  • R-Value Observed: 0.252 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 161.19α = 90
b = 53.85β = 111.47
c = 176.62γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
XSCALEdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Human Genome Research Institute (NIH/NHGRI)United StatesNIH grant AR-067288

Revision History  (Full details and data files)

  • Version 1.0: 2019-12-11
    Type: Initial release
  • Version 1.1: 2020-03-11
    Changes: Data collection, Database references
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Advisory, Atomic model, Data collection, Derived calculations, Structure summary
  • Version 2.1: 2023-10-11
    Changes: Data collection, Database references, Derived calculations, Refinement description, Structure summary