Calorimetric investigation of the domain structure of human complement Cl-s: reversible unfolding of the short consensus repeat units.


Abstract

Cl-s is a multidomain serine protease that participates in Ca2+-dependent protein-protein interactions with other subcomponents of Cl, the first component of human complement. Proteolytically derived fragments that retain some of the functional properties of the parent protein have been isolated, and their thermal stability has been investigated by differential scanning calorimetry. Three endothermic transitions are observed in whole Cl-s near 37, 49, and 60 degrees C in 0.05 M Tris-HCl, pH 7.2, containing 0.22 M NaCl and 0.1 mM EDTA. The first (37 degrees C) and third (60 degrees C) transitions are also seen in Cl-s-A, a derivative comprised mainly of the intact nonenzymatic A chain. The second (49 degrees C) and third transitions are seen in Cl-s-gamma B, a fragment comprised of the intact B chain, disulfide linked to the C-terminal gamma region of the A chain. Thus, the first transition, which is alone stabilized by Ca2+, corresponds to the melting of the N-terminal alpha beta region of the A chain, the second to the melting of the catalytic B chain domain, and the third to the gamma region. The gamma region is comprised of two homologous short consensus repeat (SCR) motifs that are also found in several other complement and coagulation proteins. A new 24-kDa fragment, Cl-s-gamma, which contains these two SCRs, was isolated from plasmic and chymotryptic digests of Cl-s-A. Cl-s-gamma exhibits a reversible transition near 60 degrees C corresponding to the highest temperature peak in whole Cl-s and Cl-s-A.(ABSTRACT TRUNCATED AT 250 WORDS) Study holds ProTherm entries: 3835 Extra Details: additive : EDTA(0.1 mM), short consensus repeat units; multidomain serine protease;,endothermic transitions; folded domains

Submission Details

ID: R6pUyUVs3

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:22 p.m.

Version: 1

Publication Details
Medved LV;Busby TF;Ingham KC,Biochemistry (1989) Calorimetric investigation of the domain structure of human complement Cl-s: reversible unfolding of the short consensus repeat units. PMID:2528372
Additional Information

Structure view and single mutant data analysis

Study data

No weblogo for data of varying length.
Colors: D E R H K S T N Q A V I L M F Y W C G P
 

Data Distribution

Studies with similar sequences (approximate matches)

Correlation with other assays (exact sequence matches)


Relevant PDB Entries

Structure ID Release Date Resolution Structure Title
1NZI 2003-06-10 1.5 Crystal Structure of the CUB1-EGF Interaction Domain of Complement Protease C1s
1ELV 2001-03-14 1.7 CRYSTAL STRUCTURE OF THE CATALYTIC DOMAIN OF HUMAN COMPLEMENT C1S PROTEASE
4LOS 2013-08-07 2.0 C1s CUB2-CCP1
4LOR 2013-08-07 2.5 C1s CUB1-EGF-CUB2 in complex with a collagen-like peptide from C1q
5UBM 2017-11-08 2.5 Crystal structure of human C1s in complex with inhibitor gigastasin
4J1Y 2013-04-24 2.66 The X-ray crystal structure of human complement protease C1s zymogen
4LOT 2013-08-07 2.92 C1s CUB2-CCP1-CCP2
4LMF 2013-08-07 2.92 C1s CUB1-EGF-CUB2
6F1C 2018-01-17 4.2 C1rC1s complex
6F1H 2018-01-17 4.5 C1rC1s complex

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
100.0 Complement C1s subcomponent P09871 C1S_HUMAN