Location of 3-hydroxyproline residues in collagen types I, II, III, and V/XI implies a role in fibril supramolecular assembly.
Collagen triple helices are stabilized by 4-hydroxyproline residues. No function is known for the much less common 3-hydroxyproline (3Hyp), although genetic defects inhibiting its formation cause recessive osteogenesis imperfecta. To help understand the pathogenesis, we used mass spectrometry to identify the sites and local sequence motifs of 3Hyp residues in fibril-forming collagens from normal human and bovine tissues. The results confirm a single, essentially fully occupied 3Hyp site (A1) at Pro(986) in A-clade chains alpha1(I), alpha1(II), and alpha2(V). Two partially modified sites (A2 and A3) were found at Pro(944) in alpha1(II) and alpha2(V) and Pro(707) in alpha2(I) and alpha2(V), which differed from A1 in sequence motif. Significantly, the distance between sites 2 and 3, 237 residues, is close to the collagen D-period (234 residues). A search for additional D-periodic 3Hyp sites revealed a fourth site (A4) at Pro(470) in alpha2(V), 237 residues N-terminal to site 3. In contrast, human and bovine type III collagen contained no 3Hyp at any site, despite a candidate proline residue and recognizable A1 sequence motif. A conserved histidine in mammalian alpha1(III) at A1 may have prevented 3-hydroxylation because this site in chicken type III was fully hydroxylated, and tyrosine replaced histidine. All three B-clade type V/XI collagen chains revealed the same three sites of 3Hyp but at different loci and sequence contexts from those in A-clade collagen chains. Two of these B-clade sites were spaced apart by 231 residues. From these and other observations we propose a fundamental role for 3Hyp residues in the ordered self-assembly of collagen supramolecular structures.
Weis
Mary Ann
MA
Orthopaedic Research Laboratories, Department of Orthopaedics and Sports Medicine, University of Washington, Seattle, Washington 98195-6500, USA.
Hudson
David M
DM
Kim
Lammy
L
Scott
Melissa
M
Wu
Jiann-Jiu
JJ
Eyre
David R
DR
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D001842:Bone and Bones / Q000737:chemistry / Q000378:metabolism; D002356:Cartilage / Q000737:chemistry / Q000378:metabolism; D002417:Cattle; D002645:Chickens; D003094:Collagen / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D024042:Collagen Type I / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D024043:Collagen Type II / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D024061:Collagen Type III / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D024062:Collagen Type V / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D024161:Collagen Type XI / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006909:Hydroxyproline / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D053719:Tandem Mass Spectrometry; D055815:Young Adult
D024042:Collagen Type I; D024043:Collagen Type II; D024061:Collagen Type III; D024062:Collagen Type V; D024161:Collagen Type XI; D016326:Extracellular Matrix Proteins; C026215:3-hydroxyproline; D003094:Collagen; D006909:Hydroxyproline