1XWD

Crystal Structure of Human Follicle Stimulating Hormone Complexed with its Receptor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.92 Å
  • R-Value Free: 0.259 
  • R-Value Work: 0.219 
  • R-Value Observed: 0.221 

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This is version 2.1 of the entry. See complete history


Literature

Structure of human follicle-stimulating hormone in complex with its receptor.

Fan, Q.R.Hendrickson, W.A.

(2005) Nature 433: 269-277

  • DOI: https://doi.org/10.1038/nature03206
  • Primary Citation of Related Structures:  
    1XWD

  • PubMed Abstract: 

    Follicle-stimulating hormone (FSH) is central to reproduction in mammals. It acts through a G-protein-coupled receptor on the surface of target cells to stimulate testicular and ovarian functions. We present here the 2.9-A-resolution structure of a partially deglycosylated complex of human FSH bound to the extracellular hormone-binding domain of its receptor (FSHR(HB)). The hormone is bound in a hand-clasp fashion to an elongated, curved receptor. The buried interface of the complex is large (2,600 A2) and has a high charge density. Our analysis suggests that all glycoprotein hormones bind to their receptors in this mode and that binding specificity is mediated by key interaction sites involving both the common alpha- and hormone-specific beta-subunits. On binding, FSH undergoes a concerted conformational change that affects protruding loops implicated in receptor activation. The FSH-FSHR(HB) complexes form dimers in the crystal and at high concentrations in solution. Such dimers may participate in transmembrane signal transduction.


  • Organizational Affiliation

    Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032, USA.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Glycoprotein hormones alpha chain
A, D
92Homo sapiensMutation(s): 0 
Gene Names: CGA
UniProt & NIH Common Fund Data Resources
Find proteins for P01215 (Homo sapiens)
Explore P01215 
Go to UniProtKB:  P01215
PHAROS:  P01215
GTEx:  ENSG00000135346 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP01215
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Follitropin beta chain
B, E
111Homo sapiensMutation(s): 0 
Gene Names: FSHB
UniProt & NIH Common Fund Data Resources
Find proteins for P01225 (Homo sapiens)
Explore P01225 
Go to UniProtKB:  P01225
PHAROS:  P01225
GTEx:  ENSG00000131808 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP01225
Sequence Annotations
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  • Reference Sequence
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
Follicle stimulating hormone receptor
C, F
252Homo sapiensMutation(s): 0 
Gene Names: FSHR
UniProt & NIH Common Fund Data Resources
Find proteins for P23945 (Homo sapiens)
Explore P23945 
Go to UniProtKB:  P23945
PHAROS:  P23945
GTEx:  ENSG00000170820 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP23945
Sequence Annotations
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  • Reference Sequence
Oligosaccharides

Help

Entity ID: 4
MoleculeChains Length2D Diagram Glycosylation3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
G
2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G42666HT
GlyCosmos:  G42666HT
GlyGen:  G42666HT
Entity ID: 5
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
H
3N-Glycosylation
Glycosylation Resources
GlyTouCan:  G15407YE
GlyCosmos:  G15407YE
GlyGen:  G15407YE
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NAG
Query on NAG

Download Ideal Coordinates CCD File 
I [auth A]
J [auth A]
K [auth B]
L [auth B]
P [auth D]
I [auth A],
J [auth A],
K [auth B],
L [auth B],
P [auth D],
Q [auth E]
2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
M [auth B],
N [auth B],
O [auth C]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.92 Å
  • R-Value Free: 0.259 
  • R-Value Work: 0.219 
  • R-Value Observed: 0.221 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 121.33α = 90
b = 66.938β = 99.13
c = 148.629γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
DENZOdata reduction
SCALEPACKdata scaling
AMoREphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2005-01-25
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Advisory, Version format compliance
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Advisory, Atomic model, Data collection, Derived calculations, Structure summary
  • Version 2.1: 2023-08-23
    Changes: Data collection, Database references, Refinement description, Structure summary