5IKU

Crystal structure of the Hathewaya histolytica ColG tandem collagen-binding domain s3as3b in the presence of calcium at 1.9 Angstrom resolution

Summary for 5IKU

• Entry DOI: 10.2210/pdb5iku/pdb
• Descriptor: Collagenase, CALCIUM ION (3 entities in total)
• Functional Keywords: calcium-binding protein collagen-binding protein, protein binding
• Biological source: Hathewaya histolytica
• Total number of polymer chains: 1
• Total formula weight: 27007.74

Authors

Janowska, K.,Bauer, R.,Roeser, R.,Sakon, J.,Matsushita, O. (deposition date: 2016-03-03, release date: 2017-03-15, Last modification date: 2024-03-06)

Primary citation

Caviness, P.,Bauer, R.,Tanaka, K.,Janowska, K.,Roeser, J.R.,Harter, D.,Sanders, J.,Ruth, C.,Matsushita, O.,Sakon, J.
Ca2+-induced orientation of tandem collagen binding domains from clostridial collagenase ColG permits two opposing functions of collagen fibril formation and retardation.
Febs J., 285:3254-3269, 2018

PubMed Abstract: To penetrate host tissues, histotoxic clostridia secrete virulence factors including enzymes to hydrolyze extracellular matrix. Clostridium histolyticum, recently renamed as Hathewaya histolytica, produces two classes of collagenase (ColG and ColH). The high-speed AFM study showed that ColG collagenase moves unidirectionally to plane collagen fibril and rebundles fibril when stalled . The structural explanation of the roles for the tandem collagen-binding segment (CBDs) is illuminated by its calcium-bound crystal structure at 1.9 Å resolution (R = 15.0%; R = 19.6%). Activation may involve calcium-dependent domain rearrangement supported by both small-angle X-ray scattering and size exclusion chromatography. At pCa ≥ 5 (pCa = -log[Ca ]), the tandem CBD adopts an extended conformation that may facilitate secretion from the bacterium. At pCa ≤ 4, the compact structure seen in the crystal structure is adopted. This arrangement positions the two binding surfaces ~ 55 Å apart, and possibly ushers ColG along tropocollagen molecules that allow for unidirectional movement. A sequential binding mode where tighter binding CBD2 binds first could aid in processivity as well. Switch from processive collagenolysis to fibril rearrangement could be concentration dependent. Collagen fibril formation is retarded at 1 : 1 molar ratio of tandem CBD to collagen. Tandem CBD may help isolate a tropocollagen molecule from a fibril at this ratio. At 0.1 : 1 to 0.5 : 1 molar ratios fibril self-assembly was accelerated. Gain of function as a result of gene duplication of CBD for the M9B enzymes is speculated. The binding and activation modes described here will aid in drug delivery design.

PubMed: 30035850
DOI: 10.1111/febs.14611

Experimental method

X-RAY DIFFRACTION (1.9 Å)