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PMID: 9096363 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Folding of the beta-propeller domain of the integrin alphaL subunit is independent of the I domain and dependent on the beta2 subunit.

Huang C, Springer TA

Abstract

We have studied the folding during biosynthesis of the lymphocyte function-associated antigen 1 (LFA-1) alphaL subunit using mAb to epitopes that map to seven different regions within the amino acid sequence. The N-terminal portion of alphaL is predicted to contain a beta-propeller domain, consisting of seven beta-sheets, and an I domain that is predicted to be inserted between beta-sheet 2 and beta-sheet 3 of the beta-propeller. The I domain of alphaL folds before association with the beta2 subunit, as shown by immunoprecipitation of the unassociated alphaL subunit by mAbs specific for four different sequence elements within the I domain. By contrast, the beta-propeller domain is not folded in unassociated alphaL after a chase of as long as 12 h after synthesis, but does fold upon association with beta2. This is shown with mAbs to regions of alphaL, that precede and follow the I domain in the primary structure. A mAb that maps near the junction of the C terminus of the I domain with the beta-propeller domain suggests that this region is partially folded before subunit association. The results show that the I domain and beta-propeller domains fold independently of one another, and suggest that the beta-propeller domain bears an interface for association with the beta subunit.

MeSH Terms
Antibodies, Monoclonal/immunology CD18 Antigens/biosynthesis,chemistry,immunology Cell Line, Transformed Lymphocyte Function-Associated Antigen-1/biosynthesis,chemistry,immunology Protein Folding
Chemicals
Antibodies, Monoclonal CD18 Antigens Lymphocyte Function-Associated Antigen-1
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Huang C
Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Springer T A
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44 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1997-04-01
Pages
3162-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC20339
Subset
IM
Grants
NCI NIH HHS · R01 CA031798 · United States
NCI NIH HHS · R37 CA031798 · United States
NCI NIH HHS · CA31798 · United States
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