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Anti-ADAM 10, C-terminus antibody

RRID:AB_2242320

Antibody ID

AB_2242320

Target Antigen

ADAM 10 C-terminus b, h, m, r

Proper Citation

(Millipore Cat# AB19026, RRID:AB_2242320)

Clonality

polyclonal antibody

Comments

seller recommendations: Western Blot; WB

Host Organism

rabbit

Vendor

Millipore

Cat Num

AB19026

Publications that use this research resource

Structural Basis for Regulated Proteolysis by the α-Secretase ADAM10.

  • Seegar TCM
  • Cell
  • 2017 Dec 14

Literature context:


Abstract:

Cleavage of membrane-anchored proteins by ADAM (a disintegrin and metalloproteinase) endopeptidases plays a key role in a wide variety of biological signal transduction and protein turnover processes. Among ADAM family members, ADAM10 stands out as particularly important because it is both responsible for regulated proteolysis of Notch receptors and catalyzes the non-amyloidogenic α-secretase cleavage of the Alzheimer's precursor protein (APP). We present here the X-ray crystal structure of the ADAM10 ectodomain, which, together with biochemical and cellular studies, reveals how access to the enzyme active site is regulated. The enzyme adopts an unanticipated architecture in which the C-terminal cysteine-rich domain partially occludes the enzyme active site, preventing unfettered substrate access. Binding of a modulatory antibody to the cysteine-rich domain liberates the catalytic domain from autoinhibition, enhancing enzymatic activity toward a peptide substrate. Together, these studies reveal a mechanism for regulation of ADAM activity and offer a roadmap for its modulation.

Funding information:
  • NCI NIH HHS - P01 CA119070()
  • NCI NIH HHS - R01 CA092433()
  • NCI NIH HHS - R35 CA220340()
  • NHLBI NIH HHS - T32 HL007627()
  • NIA NIH HHS - R01 AG016379(United States)
  • NIGMS NIH HHS - P41 GM103403()
  • NINDS NIH HHS - R01 NS038486()