Unknown

Dataset Information

0

Identification of a PAI-1-binding site within an intrinsically disordered region of vitronectin.


ABSTRACT: The serine protease inhibitor, plasminogen activator inhibitor Type-1 (PAI-1) is a metastable protein that undergoes an unusual transition to an inactive conformation with a short half-life of only 1-2?hr. Circulating PAI-1 is bound to a cofactor vitronectin, which stabilizes PAI-1 by slowing this latency conversion. A well-characterized PAI-1-binding site on vitronectin is located within the somatomedin B (SMB) domain, corresponding to the first 44 residues of the protein. Another PAI-1 recognition site has been identified with an engineered form of vitronectin lacking the SMB domain, yet retaining PAI-1 binding capacity (Schar, Blouse, Minor, Peterson. J Biol Chem. 2008;283:28487-28496). This additional binding site is hypothesized to lie within an intrinsically disordered domain (IDD) of vitronectin. To localize the putative binding site, we constructed a truncated form of vitronectin containing 71 amino acids from the N-terminus, including the SMB domain and an additional 24 amino acids from the IDD region. This portion of the IDD is rich in acidic amino acids, which are hypothesized to be complementary to several basic residues identified within an extensive vitronectin-binding site mapped on PAI-1 (Schar, Jensen, Christensen, Blouse, Andreasen, Peterson. J Biol Chem. 2008;283:10297-10309). Steady-state and stopped-flow fluorescence measurements demonstrate that the truncated form of vitronectin exhibits the same rapid biphasic association as full-length vitronectin and that the IDD hosts the elusive second PAI-1 binding site that lies external to the SMB domain of vitronectin.

SUBMITTER: Chu Y 

PROVIDER: S-EPMC6954738 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

altmetric image

Publications

Identification of a PAI-1-binding site within an intrinsically disordered region of vitronectin.

Chu Yuzhuo Y   Bucci Joel C JC   Peterson Cynthia B CB  

Protein science : a publication of the Protein Society 20191120 2


The serine protease inhibitor, plasminogen activator inhibitor Type-1 (PAI-1) is a metastable protein that undergoes an unusual transition to an inactive conformation with a short half-life of only 1-2 hr. Circulating PAI-1 is bound to a cofactor vitronectin, which stabilizes PAI-1 by slowing this latency conversion. A well-characterized PAI-1-binding site on vitronectin is located within the somatomedin B (SMB) domain, corresponding to the first 44 residues of the protein. Another PAI-1 recogni  ...[more]

Similar Datasets

| S-EPMC8593223 | biostudies-literature
| S-EPMC7692026 | biostudies-literature
| S-EPMC2782050 | biostudies-literature
| S-EPMC6164615 | biostudies-literature
| S-EPMC4380367 | biostudies-literature
| S-EPMC8604960 | biostudies-literature
| S-EPMC7415685 | biostudies-literature
2023-11-09 | GSE247419 | GEO
| S-EPMC7392517 | biostudies-literature
| S-EPMC4446436 | biostudies-literature